Is DNHD1 p.Ala4412Ser (c.13234G>T) pathogenic?

DNHD1 p.Ala4412Ser (c.13234G>T) is classified Uncertain significance in DNHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-20). AlphaMissense: likely benign (0.0849); Very rare (popmax 0.00017%, nfe).

How common is DNHD1 p.Ala4412Ser (c.13234G>T) in the general population?

DNHD1 p.Ala4412Ser (c.13234G>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about DNHD1 p.Ala4412Ser (c.13234G>T)?

AlphaMissense predicts likely benign (score 0.0849) — an in-silico prediction, not a clinical call.

DNHD1 p.Ala4412Ser

c.13234G>T · VCV4013796

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0849 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0849	likely benign
REVEL	0.079	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 1	GERP -0.51
Regional constraint	o/e 1.05	unconstrained · MANE · 3,234 bp · p 0.2 · regional, not allelic
Overall
CADD	10.15	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,178,946 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,611,516 alleles · very rare

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.Ala4412Ser
Coding: c.13234G>T
MANE Select: NM_144666
Type: single nucleotide variant
Location: chr11:6570746 (GRCh38)
Gene constraint: LOEUF 0.897 · pLI <0.01 (gnomAD)
Residue 4412: 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.Arg3978Ter Pathogenic/Likely pathogenic ★★ same type
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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-ala4412ser (accessed [today's date]).

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