Is DNAH7 p.Arg688Trp (c.2062C>T) pathogenic?

DNAH7 p.Arg688Trp (c.2062C>T) is classified Uncertain significance in DNAH7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). AlphaMissense: ambiguous (0.5062); Ultra-rare (popmax 0.0334%, mid).

How common is DNAH7 p.Arg688Trp (c.2062C>T) in the general population?

DNAH7 p.Arg688Trp (c.2062C>T) is ultra-rare (popmax 0.0334%, mid) (gnomAD).

What do computational predictors say about DNAH7 p.Arg688Trp (c.2062C>T)?

AlphaMissense predicts ambiguous (score 0.5062) — an in-silico prediction, not a clinical call.

DNAH7 p.Arg688Trp

c.2062C>T · VCV4661063

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5062 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, mid)

Computational evidence

Protein change
AlphaMissense	0.5062	ambiguous
REVEL	0.323	indeterminate
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.91 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.5	GERP 1.8, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 331 kb · p 0.14 · regional, not allelic
Overall
CADD	24.3	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 0.0334% Middle Eastern · 2/5,990 alleles

Filtering AF 0.00588% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00382%

Overall 0.00477% 76/1,591,794 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0334%	2,995
African / African-American	0.0095%	10,530
Remaining individualsnot grpmax-eligible	0.00649%	15,398
European (non-Finnish)	0.00528%	18,922
Finnishnot grpmax-eligible	0.00157%	63,750

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.Arg688Trp
Coding: c.2062C>T
MANE Select: NM_018897
Type: single nucleotide variant
Location: chr2:195970091 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)
Residue 688: the 'stem' region

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

Similar variants

DNAH7 p.Arg688= Likely benign same residue
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

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-arg688trp (accessed [today's date]).

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