Is DNHD1 p.Asn694Ser (c.2081A>G) pathogenic?

DNHD1 p.Asn694Ser (c.2081A>G) is classified Benign in DNHD1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-03-14). AlphaMissense: likely benign (0.0779); Common (popmax 87%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about DNHD1 p.Asn694Ser (c.2081A>G)?

AlphaMissense predicts likely benign (score 0.0779) — an in-silico prediction, not a clinical call.

DNHD1 p.Asn694Ser

Q: How common is DNHD1 p.Asn694Ser (c.2081A>G) in the general population?

DNHD1 p.Asn694Ser (c.2081A>G) is common (popmax 87%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2081A>G · rs7480644 · VCV1287986

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0779 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 87%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0779	likely benign
REVEL	0.002	strongly 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 0.28	GERP -3.8
Regional constraint	o/e 0.90	unconstrained · MANE · 66 kb · p 5.3e-11 · regional, not allelic
Overall
CADD	1.548	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 87% East Asian · 35,568/40,872 alleles

Filtering AF 86.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 86%

Overall 68% 1,055,203/1,550,856 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	87%	1
South Asian	76.6%	1
Ashkenazi Jewishnot grpmax-eligible	73%	1
Middle Eastern	71%	1
Remaining individualsnot grpmax-eligible	70.4%	1
Finnishnot grpmax-eligible	68.2%	1
African / African-American	67.5%	1
European (non-Finnish)	66.8%	1
Admixed American	62.4%	2
Amishnot grpmax-eligible	54.8%	2

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.Asn694Ser
Coding: c.2081A>G
MANE Select: NM_144666
dbSNP: rs7480644
Type: single nucleotide variant
Location: chr11:6528765 (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
DNHD1 p.Arg2555Trp 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/dnhd1-p-asn694ser (accessed [today's date]).

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