Is DNAH5 p.Leu2862Phe (c.8586G>T) pathogenic?

DNAH5 p.Leu2862Phe (c.8586G>T) is classified Benign/Likely benign in DNAH5 (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0979); Common (popmax 37.9%, mid) — too common for a highly-penetrant pathogenic allele; Associated with primary ciliary dyskinesia.

What condition is associated with DNAH5 p.Leu2862Phe (c.8586G>T)?

DNAH5 p.Leu2862Phe (c.8586G>T) is associated with primary ciliary dyskinesia, primary ciliary dyskinesia 3 (ClinVar).

How is Primary ciliary dyskinesia inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DNAH5 p.Leu2862Phe (c.8586G>T)?

AlphaMissense predicts likely benign (score 0.0979) — an in-silico prediction, not a clinical call.

DNAH5 p.Leu2862Phe

Q: How common is DNAH5 p.Leu2862Phe (c.8586G>T) in the general population?

DNAH5 p.Leu2862Phe (c.8586G>T) is common (popmax 37.9%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.8586G>T · rs10513155 · VCV178745

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

AlphaMissense

likely benign

0.0979 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 37.9%, mid) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.0979	likely benign
REVEL	0.097	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.25	GERP 0.71, phastCons 0.2
Regional constraint	o/e 0.98	unconstrained · MANE · 228 kb · p 0.16 · regional, not allelic
Overall
CADD	8.424	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 37.9% Middle Eastern · 2,296/6,062 alleles

Filtering AF 36.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 36.1%

Overall 26.6% 429,352/1,613,654 alleles · common

Ancestry group	Frequency	1 in
Middle Easterngrpmax	37.9%	3
Amishnot grpmax-eligible	37.1%	3
Ashkenazi Jewishnot grpmax-eligible	33.3%	3
European (non-Finnish)	27.9%	4
Remaining individualsnot grpmax-eligible	27.7%	4
Admixed American	25.7%	4
South Asian	22.4%	4
Finnishnot grpmax-eligible	21.8%	5
East Asian	18.5%	5
African / African-American	16.7%	6

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DNAH5
Protein: p.Leu2862Phe
Coding: c.8586G>T
MANE Select: NM_001369
dbSNP: rs10513155
Type: single nucleotide variant
Location: chr5:13788777 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2862: a UniProt-annotated variant site (in)

Full DNAH5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

primary ciliary dyskinesia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: primary ciliary dyskinesia 3

For Primary ciliary dyskinesia (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Neonatal
Prevalence: 1-5 / 10 000 (Pakistan)

Similar variants

DNAH5 p.Leu2862Ser Uncertain significance ★ ⚠ same residue
DNAH5 p.Leu2862= Likely benign ★ same residue
DNAH5 c.10555+1G>C Likely pathogenic ★★ same condition
DNAH5 c.1089+1G>A Pathogenic ★★ same condition
DNAH5 c.11028+2T>C Pathogenic/Likely pathogenic ★★ same condition
DNAH5 c.11029-2A>T Pathogenic/Likely pathogenic ★★ same condition
DNAH5 c.11571-1G>A Pathogenic ★★ same condition
DNAH5 c.12910-1G>C Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dnah5-p-leu2862phe (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown