Is DNAJC1 p.Ala263Ser (c.787G>T) pathogenic?

DNAJC1 p.Ala263Ser (c.787G>T) is classified Uncertain significance in DNAJC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-22). AlphaMissense: likely benign (0.0984); Very rare (popmax 0.00127%, nfe).

How common is DNAJC1 p.Ala263Ser (c.787G>T) in the general population?

DNAJC1 p.Ala263Ser (c.787G>T) is very rare (popmax 0.00127%, nfe) (gnomAD).

What do computational predictors say about DNAJC1 p.Ala263Ser (c.787G>T)?

AlphaMissense predicts likely benign (score 0.0984) — an in-silico prediction, not a clinical call.

DNAJC1 p.Ala263Ser

c.787G>T · VCV4013565

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0984 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00127%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0984	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -6.79	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 4.9	GERP 2.4, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 247 kb · p 0.65 · regional, not allelic
Overall
CADD	21.9	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 0.00127% European (non-Finnish) · 15/1,176,984 alleles

Filtering AF 0.000765% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000607%

Overall 0.000933% 15/1,606,968 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: DNAJC1
Protein: p.Ala263Ser
Coding: c.787G>T
MANE Select: NM_022365
Type: single nucleotide variant
Location: chr10:21904555 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.45 · 2 PDB

Full DNAJC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJC1 p.Ala3Thr Uncertain significance ★ ⚠ same type
DNAJC1 p.Ala417Gly Uncertain significance ★ ⚠ same type
DNAJC1 p.Ala455Val Uncertain significance ★ ⚠ same type
DNAJC1 p.Ala490Gly Uncertain significance ★ ⚠ same type
DNAJC1 p.Ala524Ser Uncertain significance ★ ⚠ same type
DNAJC1 p.Ala537Thr Uncertain significance ★ ⚠ same type
DNAJC1 p.Arg107Thr Uncertain significance ★ ⚠ same type
DNAJC1 p.Arg321Gln 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/dnajc1-p-ala263ser (accessed [today's date]).

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