Is DNAH7 p.Phe3347Leu (c.10041T>A) pathogenic?

DNAH7 p.Phe3347Leu (c.10041T>A) is classified Uncertain significance in DNAH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-27). AlphaMissense: likely pathogenic (0.8064); Ultra-rare (popmax 0.0175%, nfe).

How common is DNAH7 p.Phe3347Leu (c.10041T>A) in the general population?

DNAH7 p.Phe3347Leu (c.10041T>A) is ultra-rare (popmax 0.0175%, nfe) (gnomAD).

What do computational predictors say about DNAH7 p.Phe3347Leu (c.10041T>A)?

AlphaMissense predicts likely pathogenic (score 0.8064) — an in-silico prediction, not a clinical call.

DNAH7 p.Phe3347Leu

c.10041T>A · VCV4661055

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8064 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0175%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.8064	likely pathogenic
REVEL	0.244	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.1	GERP -3.5
Regional constraint	o/e 1.02	unconstrained · MANE · 331 kb · p 0.14 · regional, not allelic
Overall
CADD	15.64	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 0.0175% European (non-Finnish) · 207/1,179,944 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0148%

Overall 0.0134% 216/1,613,914 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0175%	5,700
Remaining individualsnot grpmax-eligible	0.0128%	7,810
African / African-American	0.00133%	74,934

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.Phe3347Leu
Coding: c.10041T>A
MANE Select: NM_018897
Type: single nucleotide variant
Location: chr2:195808724 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)

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-phe3347leu (accessed [today's date]).

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