Is DNHD1 p.Arg3421His (c.10262G>A) pathogenic?

DNHD1 p.Arg3421His (c.10262G>A) is classified Likely benign in DNHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-08). AlphaMissense: likely benign (0.0578); Very rare (popmax 0.00833%, sas).

How common is DNHD1 p.Arg3421His (c.10262G>A) in the general population?

DNHD1 p.Arg3421His (c.10262G>A) is very rare (popmax 0.00833%, sas) (gnomAD).

What do computational predictors say about DNHD1 p.Arg3421His (c.10262G>A)?

AlphaMissense predicts likely benign (score 0.0578) — an in-silico prediction, not a clinical call.

DNHD1 p.Arg3421His

c.10262G>A · rs528267237 · VCV2365548

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0578 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0578	likely benign
REVEL	0.076	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 4.3	GERP 0.33, phastCons 0.17
Regional constraint	o/e 0.90	unconstrained · MANE · 66 kb · p 5.3e-11 · regional, not allelic
Overall
CADD	2.163	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 0.00833% South Asian · 7/84,064 alleles

Filtering AF 0.00385% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00272%

Overall 0.00103% 16/1,551,100 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00833%	12,009
Finnishnot grpmax-eligible	0.00503%	19,873
Remaining individualsnot grpmax-eligible	0.00499%	20,039
Admixed American	0.00196%	51,016
African / African-American	0.00137%	73,162
European (non-Finnish)	8.72e-05%	1,146,668

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.Arg3421His
Coding: c.10262G>A
MANE Select: NM_144666
dbSNP: rs528267237
Type: single nucleotide variant
Location: chr11:6564102 (GRCh38)
Gene constraint: LOEUF 0.897 · pLI <0.01 (gnomAD)
Residue 3421: a UniProt-annotated variant site (in spgf65); a UniProt-annotated variant site (in spgf65; low expression, if any, in sperm flagella)

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

Similar variants

DNHD1 p.Arg3421Cys 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-arg3421his (accessed [today's date]).

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