Is DNHD1 p.Arg3247Pro (c.9740G>C) pathogenic?

DNHD1 p.Arg3247Pro (c.9740G>C) is classified Uncertain significance in DNHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely pathogenic (0.742); Rare (popmax 0.201%, afr).

How common is DNHD1 p.Arg3247Pro (c.9740G>C) in the general population?

DNHD1 p.Arg3247Pro (c.9740G>C) is rare (popmax 0.201%, afr) (gnomAD).

What do computational predictors say about DNHD1 p.Arg3247Pro (c.9740G>C)?

AlphaMissense predicts likely pathogenic (score 0.742) — an in-silico prediction, not a clinical call.

DNHD1 p.Arg3247Pro

c.9740G>C · rs372291400 · VCV3084761

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.742 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.201%, afr)

Computational evidence

Protein change
AlphaMissense	0.742	likely pathogenic · top 6% in DNHD1
REVEL	0.352	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 66 kb · p 5.3e-11 · regional, not allelic
Overall
CADD	27.2	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 0.201% African / African-American · 147/73,130 alleles

Filtering AF 0.175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.164%

Overall 0.0102% 159/1,551,608 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.201%	497
Remaining individualsnot grpmax-eligible	0.0183%	5,465
European (non-Finnish)	8.72e-05%	1,146,967

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.Arg3247Pro
Coding: c.9740G>C
MANE Select: NM_144666
dbSNP: rs372291400
Type: single nucleotide variant
Location: chr11:6563452 (GRCh38)
Gene constraint: LOEUF 0.897 · pLI <0.01 (gnomAD)
Residue 3247: 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.Arg3247Gln 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-arg3247pro (accessed [today's date]).

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