Is DNAH7 p.Phe3566Ser (c.10697T>C) pathogenic?

DNAH7 p.Phe3566Ser (c.10697T>C) is classified Likely benign in DNAH7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-01). AlphaMissense: likely pathogenic (0.8792); Rare (popmax 0.452%, sas).

How common is DNAH7 p.Phe3566Ser (c.10697T>C) in the general population?

DNAH7 p.Phe3566Ser (c.10697T>C) is rare (popmax 0.452%, sas) (gnomAD).

What do computational predictors say about DNAH7 p.Phe3566Ser (c.10697T>C)?

AlphaMissense predicts likely pathogenic (score 0.8792) — an in-silico prediction, not a clinical call.

DNAH7 p.Phe3566Ser

c.10697T>C · rs111705343 · VCV723464

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.8792 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.452%, sas)

Computational evidence

Protein change
AlphaMissense	0.8792	likely pathogenic
REVEL	0.51	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 331 kb · p 0.14 · regional, not allelic
Overall
CADD	25.1	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 0.452% South Asian · 412/91,080 alleles

Filtering AF 0.416% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.402%

Overall 0.144% 2,322/1,614,158 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.679%	147
Finnishnot grpmax-eligible	0.632%	158
South Asiangrpmax	0.452%	221
Middle Eastern	0.297%	337
Remaining individualsnot grpmax-eligible	0.229%	437
Admixed American	0.123%	811
European (non-Finnish)	0.0896%	1,116
African / African-American	0.0147%	6,822
East Asian	0.00223%	44,874

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DNAH7
Protein: p.Phe3566Ser
Coding: c.10697T>C
MANE Select: NM_018897
dbSNP: rs111705343
Type: single nucleotide variant
Location: chr2:195794357 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)
Residue 3566: the 'aaa 6' region

Full DNAH7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAH7 p.Arg1884Gln Uncertain significance ★★ ⚠ same type
DNAH7 p.Arg3272Gln Uncertain significance ★★ ⚠ same type
DNAH7 p.Asn2116Ser Uncertain significance ★★ ⚠ same type
DNAH7 p.Asp1219Gly Uncertain significance ★★ ⚠ same type
DNAH7 p.Asp1787Gly Uncertain significance ★★ same type
DNAH7 p.Asp2867Tyr Uncertain significance ★★ ⚠ same type
DNAH7 p.Ile1203Met Uncertain significance ★★ ⚠ same type
DNAH7 p.Leu1715Met 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/dnah7-p-phe3566ser (accessed [today's date]).

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