Is DNAJC15 p.Ala3Ser (c.7G>T) pathogenic?

DNAJC15 p.Ala3Ser (c.7G>T) is classified Uncertain significance in DNAJC15 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-18). AlphaMissense: likely benign (0.0696); Ultra-rare (popmax 0.0134%, afr).

How common is DNAJC15 p.Ala3Ser (c.7G>T) in the general population?

DNAJC15 p.Ala3Ser (c.7G>T) is ultra-rare (popmax 0.0134%, afr) (gnomAD).

What do computational predictors say about DNAJC15 p.Ala3Ser (c.7G>T)?

AlphaMissense predicts likely benign (score 0.0696) — an in-silico prediction, not a clinical call.

DNAJC15 p.Ala3Ser

c.7G>T · VCV3841525

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0696 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0696	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -5.54	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 1.7	GERP -0.47, phastCons 0.065
Regional constraint	o/e 1.11	unconstrained · MANE · 84 kb · p 0.13 · regional, not allelic
Overall
CADD	10.09	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 0.0134% African / African-American · 10/74,840 alleles

Filtering AF 0.00724% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00551%

Overall 0.000683% 11/1,610,360 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0134%	7,484
European (non-Finnish)	8.49e-05%	1,178,543

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: DNAJC15
Protein: p.Ala3Ser
Coding: c.7G>T
MANE Select: NM_013238
Type: single nucleotide variant
Location: chr13:43023633 (GRCh38)
Gene constraint: LOEUF 1.634 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.66

Full DNAJC15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJC15 p.Ala3Thr Uncertain significance ★ ⚠ same residue
DNAJC15 p.Ala3Val Uncertain significance ★ ⚠ same residue
DNAJC15 p.Ala2Val Uncertain significance ★ ⚠ same type
DNAJC15 p.Ala49Gly Uncertain significance ★ ⚠ same type
DNAJC15 p.Ala49Val Uncertain significance ★ ⚠ same type
DNAJC15 p.Ala51Thr Uncertain significance ★ ⚠ same type
DNAJC15 p.Ala72Val Uncertain significance ★ ⚠ same type
DNAJC15 p.Ala8Pro 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/dnajc15-p-ala3ser (accessed [today's date]).

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