Is DNAJC8 p.Ser10Leu (c.29C>T) pathogenic?

DNAJC8 p.Ser10Leu (c.29C>T) is classified Uncertain significance in DNAJC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-24). AlphaMissense: likely benign (0.0969); Very rare (popmax 0.00134%, afr).

How common is DNAJC8 p.Ser10Leu (c.29C>T) in the general population?

DNAJC8 p.Ser10Leu (c.29C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about DNAJC8 p.Ser10Leu (c.29C>T)?

AlphaMissense predicts likely benign (score 0.0969) — an in-silico prediction, not a clinical call.

DNAJC8 p.Ser10Leu

c.29C>T · VCV3841596

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0969 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0969	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -8.64	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 9.6	GERP 2, phastCons 1
Regional constraint	o/e 1.50	unconstrained · MANE · 73 bp · p 0.0044 · regional, not allelic
Overall
CADD	23.2	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 0.00134% African / African-American · 1/74,886 alleles

Overall 0.000124% 2/1,612,924 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,886
European (non-Finnish)	8.47e-05%	1,179,999

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.Ser10Leu
Coding: c.29C>T
MANE Select: NM_014280
Type: single nucleotide variant
Location: chr1:28232970 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.60 · 1 PDB

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.Ala93Val 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

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-ser10leu (accessed [today's date]).

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