Is DNAH5 p.Pro4488Thr (c.13462C>A) pathogenic?

DNAH5 p.Pro4488Thr (c.13462C>A) is classified Benign in DNAH5 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). AlphaMissense: ambiguous (0.5141); Common (popmax 12.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with primary ciliary dyskinesia.

What condition is associated with DNAH5 p.Pro4488Thr (c.13462C>A)?

DNAH5 p.Pro4488Thr (c.13462C>A) 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.Pro4488Thr (c.13462C>A)?

AlphaMissense predicts ambiguous (score 0.5141) — an in-silico prediction, not a clinical call.

DNAH5 p.Pro4488Thr

Q: How common is DNAH5 p.Pro4488Thr (c.13462C>A) in the general population?

DNAH5 p.Pro4488Thr (c.13462C>A) is common (popmax 12.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.13462C>A · rs113425437 · VCV226595

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

ambiguous

0.5141 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 12.8%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
AlphaMissense	0.5141	ambiguous
REVEL	0.324	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.3	GERP 1.9, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 25 kb · p 0.038 · regional, not allelic
Overall
CADD	22.9	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 12.8% African / African-American · 9,576/74,902 alleles

Filtering AF 12.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 12.5%

Overall 0.684% 11,032/1,613,832 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	12.8%	8
Admixed American	0.96%	104
Remaining individualsnot grpmax-eligible	0.917%	109
Middle Eastern	0.693%	144
South Asian	0.0472%	2,118
European (non-Finnish)	0.0187%	5,339
East Asian	0.00223%	44,852

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.Pro4488Thr
Coding: c.13462C>A
MANE Select: NM_001369
dbSNP: rs113425437
Type: single nucleotide variant
Location: chr5:13701313 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)

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.Pro4488Leu Uncertain significance ★ same residue
DNAH5 p.Pro4488= Likely benign ★ same residue
DNAH5 p.Pro4488Ser 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

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-pro4488thr (accessed [today's date]).

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