Is DNHD1 p.Gly3155Ser (c.9463G>A) pathogenic?

DNHD1 p.Gly3155Ser (c.9463G>A) is classified Benign/Likely benign in DNHD1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-08-20). AlphaMissense: likely benign (0.0709); Low-frequency (popmax 1.06%, afr).

How common is DNHD1 p.Gly3155Ser (c.9463G>A) in the general population?

DNHD1 p.Gly3155Ser (c.9463G>A) is low-frequency (popmax 1.06%, afr) (gnomAD).

What do computational predictors say about DNHD1 p.Gly3155Ser (c.9463G>A)?

AlphaMissense predicts likely benign (score 0.0709) — an in-silico prediction, not a clinical call.

DNHD1 p.Gly3155Ser

c.9463G>A · rs189381995 · VCV785338

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0709 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.06%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0709	likely benign
REVEL	0.014	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 2	GERP -0.39, phastCons 0.02
Regional constraint	o/e 0.90	unconstrained · MANE · 66 kb · p 5.3e-11 · regional, not allelic
Overall
CADD	0.674	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 1.06% African / African-American · 778/73,116 alleles

Filtering AF 1% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.977%

Overall 0.0625% 970/1,551,624 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.06%	94
Middle Eastern	0.1%	999
Admixed American	0.0941%	1,062
Remaining individualsnot grpmax-eligible	0.0782%	1,279
European (non-Finnish)	0.00776%	12,887
East Asian	0.00489%	20,459

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.Gly3155Ser
Coding: c.9463G>A
MANE Select: NM_144666
dbSNP: rs189381995
Type: single nucleotide variant
Location: chr11:6559227 (GRCh38)
Gene constraint: LOEUF 0.897 · pLI <0.01 (gnomAD)
Residue 3155: 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.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
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-gly3155ser (accessed [today's date]).

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