Is DNAH8 p.Phe2114= (c.6342T>C) pathogenic?

DNAH8 p.Phe2114= (c.6342T>C) is classified Likely benign in DNAH8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-14). Very rare (popmax 0.00355%, amr); Associated with primary ciliary dyskinesia.

What condition is associated with DNAH8 p.Phe2114= (c.6342T>C)?

DNAH8 p.Phe2114= (c.6342T>C) is associated with primary ciliary dyskinesia (ClinVar).

How common is DNAH8 p.Phe2114= (c.6342T>C) in the general population?

DNAH8 p.Phe2114= (c.6342T>C) is very rare (popmax 0.00355%, amr) (gnomAD).

How is Primary ciliary dyskinesia inherited?

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

DNAH8 p.Phe2114=

c.6342T>C · rs760696722 · VCV1935806

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00355%, amr)

Conditions

primary ciliary dyskinesia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.9	GERP 1.4, phastCons 1
Overall
CADD	8.711	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00355% Admixed American · 2/56,302 alleles

Filtering AF 0.000589% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00022%

Overall 0.000125% 2/1,602,994 alleles · very rare exomes 2/1,450,670 · genomes 0/152,324 · joint denominator

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: DNAH8
Protein: p.Phe2114=
Coding: c.6342T>C
MANE Select: NM_001206927
dbSNP: rs760696722
Type: single nucleotide variant
Location: chr6:38863904 (GRCh38)
Gene constraint: LOEUF 0.692 · pLI <0.01 (gnomAD)
Residue 2114: a UniProt-annotated variant site (found in a patient with primary ciliary dyskinesia; uncertain significance); the 'aaa 2' region

Full DNAH8 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

For Primary ciliary dyskinesia (Orphanet):

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

Similar variants

DNAH8 c.10963-1G>A Likely pathogenic ★★ same condition
DNAH8 c.11563+1G>T Likely pathogenic ★★ same condition
DNAH8 c.2664+2T>C Likely pathogenic ★★ same condition
DNAH8 c.5734-1G>T Likely pathogenic ★★ same condition
DNAH8 p.Arg1090Ter Pathogenic/Likely pathogenic ★★ same condition
DNAH8 p.Arg207Ter Pathogenic/Likely pathogenic ★★ same condition
DNAH8 p.Arg2878Ter Pathogenic ★★ same condition
DNAH8 p.Arg4166Ter 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/dnah8-p-phe2114 (accessed [today's date]).

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