Is DNHD1 p.Val703Met (c.2107G>A) pathogenic?

DNHD1 p.Val703Met (c.2107G>A) is classified Likely benign in DNHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-27). AlphaMissense: likely benign (0.0853); Very rare (popmax 0.00958%, afr).

How common is DNHD1 p.Val703Met (c.2107G>A) in the general population?

DNHD1 p.Val703Met (c.2107G>A) is very rare (popmax 0.00958%, afr) (gnomAD).

What do computational predictors say about DNHD1 p.Val703Met (c.2107G>A)?

AlphaMissense predicts likely benign (score 0.0853) — an in-silico prediction, not a clinical call.

DNHD1 p.Val703Met

c.2107G>A · rs957623735 · VCV2353973

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0853 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00958%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0853	likely benign
REVEL	0.018	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -2.9, phastCons 0.88
Regional constraint	o/e 0.90	unconstrained · MANE · 66 kb · p 5.3e-11 · regional, not allelic
Overall
CADD	2.474	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 0.00958% African / African-American · 7/73,068 alleles

Filtering AF 0.00447% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00315%

Overall 0.0018% 28/1,551,538 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00958%	10,438
Admixed American	0.00392%	25,495
South Asian	0.00357%	28,022
Remaining individualsnot grpmax-eligible	0.00333%	30,040
European (non-Finnish)	0.00122%	81,926

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: DNHD1
Protein: p.Val703Met
Coding: c.2107G>A
MANE Select: NM_144666
dbSNP: rs957623735
Type: single nucleotide variant
Location: chr11:6528881 (GRCh38)
Gene constraint: LOEUF 0.897 · pLI <0.01 (gnomAD)

Full DNHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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DNHD1 p.Glu1153Ter Pathogenic/Likely pathogenic ★★ same type
DNHD1 p.Tyr2166Ter Pathogenic/Likely pathogenic ★★ same type
DNHD1 p.Arg1582Trp Uncertain significance ★★ same type
DNHD1 p.Arg1873Ser Uncertain significance ★★ ⚠ same type
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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/dnhd1-p-val703met (accessed [today's date]).

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