Is DNHD1 p.Asp3239Asn (c.9715G>A) pathogenic?

DNHD1 p.Asp3239Asn (c.9715G>A) is classified Uncertain significance in DNHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-31). AlphaMissense: likely benign (0.3371); Ultra-rare (popmax 0.0166%, mid).

How common is DNHD1 p.Asp3239Asn (c.9715G>A) in the general population?

DNHD1 p.Asp3239Asn (c.9715G>A) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

What do computational predictors say about DNHD1 p.Asp3239Asn (c.9715G>A)?

AlphaMissense predicts likely benign (score 0.3371) — an in-silico prediction, not a clinical call.

DNHD1 p.Asp3239Asn

c.9715G>A · rs970196124 · VCV2468565

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3371 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Computational evidence

Protein change
AlphaMissense	0.3371	likely benign
REVEL	0.329	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 66 kb · p 5.3e-11 · regional, not allelic
Overall
CADD	26.2	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 0.0166% Middle Eastern · 1/6,014 alleles

Filtering AF 0.00492% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00451%

Overall 0.00509% 79/1,551,602 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,014
European (non-Finnish)	0.0061%	16,386
Remaining individualsnot grpmax-eligible	0.00499%	20,030
South Asian	0.00357%	28,023
Admixed American	0.00196%	50,990
Finnishnot grpmax-eligible	0.00167%	59,904

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.Asp3239Asn
Coding: c.9715G>A
MANE Select: NM_144666
dbSNP: rs970196124
Type: single nucleotide variant
Location: chr11:6563427 (GRCh38)
Gene constraint: LOEUF 0.897 · pLI <0.01 (gnomAD)
Residue 3239: 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

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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-asp3239asn (accessed [today's date]).

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