Is DNAJB11 p.Ala335Val (c.1004C>T) pathogenic?

DNAJB11 p.Ala335Val (c.1004C>T) is classified Uncertain significance in DNAJB11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-06). AlphaMissense: likely benign (0.1425); Very rare (popmax 0.00667%, afr).

How common is DNAJB11 p.Ala335Val (c.1004C>T) in the general population?

DNAJB11 p.Ala335Val (c.1004C>T) is very rare (popmax 0.00667%, afr) (gnomAD).

What do computational predictors say about DNAJB11 p.Ala335Val (c.1004C>T)?

AlphaMissense predicts likely benign (score 0.1425) — an in-silico prediction, not a clinical call.

DNAJB11 p.Ala335Val

c.1004C>T · VCV4697539

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1425 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1425	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -5.70	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP -0.82, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 15 kb · p 7.3e-05 · regional, not allelic
Overall
CADD	23.3	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 0.00667% African / African-American · 3/44,968 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00089%

Overall 0.00086% 12/1,394,930 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	14,989
South Asian	0.00126%	79,114
European (non-Finnish)	0.000756%	132,200

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: DNAJB11
Protein: p.Ala335Val
Coding: c.1004C>T
MANE Select: NM_016306
Type: single nucleotide variant
Location: chr3:186584581 (GRCh38)
Gene constraint: LOEUF 0.933 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.34
Residue 335: a UniProt-annotated variant site (in pkd6)

Full DNAJB11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJB11 p.Arg206Ter Pathogenic ★★ same type
DNAJB11 p.Arg242Ter Pathogenic ★★ same type
DNAJB11 p.Arg24Ter Pathogenic ★★ same type
DNAJB11 p.Arg34Ter Pathogenic ★★ same type
DNAJB11 p.Glu144Ter Pathogenic/Likely pathogenic ★★ same type
DNAJB11 p.Leu77Pro Likely pathogenic ★★ same type
DNAJB11 p.Pro54Arg Likely pathogenic ★★ same type
DNAJB11 p.Ala297Val 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/dnajb11-p-ala335val (accessed [today's date]).

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