Is DNAJC8 p.Ala93Val (c.278C>T) pathogenic?

DNAJC8 p.Ala93Val (c.278C>T) is classified Uncertain significance in DNAJC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely benign (0.0956); Ultra-rare (popmax 0.0164%, mid).

How common is DNAJC8 p.Ala93Val (c.278C>T) in the general population?

DNAJC8 p.Ala93Val (c.278C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about DNAJC8 p.Ala93Val (c.278C>T)?

AlphaMissense predicts likely benign (score 0.0956) — an in-silico prediction, not a clinical call.

DNAJC8 p.Ala93Val

c.278C>T · rs377285666 · VCV3084609

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0956 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0956	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -3.13	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 9.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 32 kb · p 3.2e-11 · regional, not allelic
Overall
CADD	23.5	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 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.0124% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0117%

Overall 0.0109% 176/1,613,666 alleles · ultra-rare exomes 165/1,461,618 · genomes 11/152,048 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
European (non-Finnish)	0.0142%	7,065
Remaining individualsnot grpmax-eligible	0.008%	12,493
Admixed American	0.00334%	29,975
Finnishnot grpmax-eligible	0.00156%	63,974

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: DNAJC8
Protein: p.Ala93Val
Coding: c.278C>T
MANE Select: NM_014280
dbSNP: rs377285666
Type: single nucleotide variant
Location: chr1:28210597 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.60 · 1 PDB
Residue 93: the j domain

Full DNAJC8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJC8 p.Ala161Thr Uncertain significance ★ ⚠ same type
DNAJC8 p.Arg95Gly Uncertain significance ★ ⚠ same type
DNAJC8 p.Asn55Ser Uncertain significance ★ same type
DNAJC8 p.Asp92Val Uncertain significance ★ ⚠ same type
DNAJC8 p.Glu179Asp Uncertain significance ★ ⚠ same type
DNAJC8 p.Glu67Lys Uncertain significance ★ ⚠ same type
DNAJC8 p.Gly11Asp Uncertain significance ★ ⚠ same type
DNAJC8 p.Gly14Asp 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/dnajc8-p-ala93val (accessed [today's date]).

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