Is DNAH17 p.Phe758= (c.2274C>T) pathogenic?

DNAH17 p.Phe758= (c.2274C>T) is classified Likely benign in DNAH17 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-01). Rare (popmax 0.123%, afr).

How common is DNAH17 p.Phe758= (c.2274C>T) in the general population?

DNAH17 p.Phe758= (c.2274C>T) is rare (popmax 0.123%, afr) (gnomAD).

DNAH17 p.Phe758=

c.2274C>T · VCV4533832

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.123%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP -0.67, phastCons 1
Overall
CADD	4.464	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.123% African / African-American · 92/75,022 alleles

Filtering AF 0.102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0948%

Overall 0.00762% 123/1,613,742 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.123%	815
Admixed American	0.0367%	2,728
Remaining individualsnot grpmax-eligible	0.0096%	10,412
South Asian	0.00329%	30,358

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: DNAH17
Protein: p.Phe758=
Coding: c.2274C>T
MANE Select: NM_173628
Type: single nucleotide variant
Location: chr17:78552710 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 (gnomAD)
Residue 758: a UniProt-annotated variant site (in spgf39); the 'stem' region

Full DNAH17 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAH17 p.Phe758Tyr Uncertain significance ★ ⚠ same residue
DNAH17 c.7752+2T>A Pathogenic/Likely pathogenic ★★ same type
DNAH17 p.Ala1014Val Uncertain significance ★★ ⚠ same type
DNAH17 p.Arg1217Thr Uncertain significance ★★ ⚠ same type
DNAH17 p.Arg2941Gln Uncertain significance ★★ same type
DNAH17 p.Arg4050Gln Uncertain significance ★★ same type
DNAH17 p.Arg4101Gln Uncertain significance ★★ ⚠ same type
DNAH17 p.Arg4246His Uncertain significance ★★ ⚠ same type

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/dnah17-p-phe758 (accessed [today's date]).

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