Is DNHD1 p.Arg1157Gln (c.3470G>A) pathogenic?

DNHD1 p.Arg1157Gln (c.3470G>A) is classified Likely benign in DNHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-01). AlphaMissense: likely benign (0.0598); Rare (popmax 0.11%, eas).

How common is DNHD1 p.Arg1157Gln (c.3470G>A) in the general population?

DNHD1 p.Arg1157Gln (c.3470G>A) is rare (popmax 0.11%, eas) (gnomAD).

What do computational predictors say about DNHD1 p.Arg1157Gln (c.3470G>A)?

AlphaMissense predicts likely benign (score 0.0598) — an in-silico prediction, not a clinical call.

DNHD1 p.Arg1157Gln

c.3470G>A · rs187615581 · VCV2204620

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0598 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.11%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0598	likely benign
REVEL	0.128	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 -2.2	GERP -3.5
Regional constraint	o/e 0.90	unconstrained · MANE · 66 kb · p 5.3e-11 · regional, not allelic
Overall
CADD	0.005	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 0.11% East Asian · 45/40,914 alleles

Filtering AF 0.0845% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0754%

Overall 0.00406% 63/1,551,726 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.11%	909
Admixed American	0.00392%	25,506
Remaining individualsnot grpmax-eligible	0.00166%	60,114
African / African-American	0.00137%	73,184
European (non-Finnish)	0.00122%	81,928

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.Arg1157Gln
Coding: c.3470G>A
MANE Select: NM_144666
dbSNP: rs187615581
Type: single nucleotide variant
Location: chr11:6539925 (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

DNHD1 p.Arg1157Pro Uncertain significance ★ same residue
DNHD1 p.Arg2928Ter Pathogenic/Likely pathogenic ★★ same type
DNHD1 p.Arg3978Ter Pathogenic/Likely pathogenic ★★ same type
DNHD1 p.Arg4048Ter Pathogenic/Likely pathogenic ★★ same type
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

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-arg1157gln (accessed [today's date]).

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