Is DNHD1 p.Arg1061Gln (c.3182G>A) pathogenic?

DNHD1 p.Arg1061Gln (c.3182G>A) is classified Uncertain significance in DNHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-13). AlphaMissense: likely benign (0.0847); Ultra-rare (popmax 0.0779%, afr).

How common is DNHD1 p.Arg1061Gln (c.3182G>A) in the general population?

DNHD1 p.Arg1061Gln (c.3182G>A) is ultra-rare (popmax 0.0779%, afr) (gnomAD).

What do computational predictors say about DNHD1 p.Arg1061Gln (c.3182G>A)?

AlphaMissense predicts likely benign (score 0.0847) — an in-silico prediction, not a clinical call.

DNHD1 p.Arg1061Gln

c.3182G>A · VCV4013764

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0847 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0779%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0847	likely benign
REVEL	0.086	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 -0.091	GERP -3.6
Regional constraint	o/e 0.90	unconstrained · MANE · 66 kb · p 5.3e-11 · regional, not allelic
Overall
CADD	6.479	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0779% African / African-American · 57/73,128 alleles

Filtering AF 0.0617% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0559%

Overall 0.00426% 66/1,548,504 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0779%	1,283
Admixed American	0.0059%	16,957
Remaining individualsnot grpmax-eligible	0.00334%	29,965
East Asian	0.00245%	40,802
European (non-Finnish)	0.000262%	381,585

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.Arg1061Gln
Coding: c.3182G>A
MANE Select: NM_144666
Type: single nucleotide variant
Location: chr11:6538667 (GRCh38)
Gene constraint: LOEUF 0.897 · pLI <0.01 (gnomAD)

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

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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-arg1061gln (accessed [today's date]).

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