Is DNAJC4 p.Leu22Phe (c.64C>T) pathogenic?

DNAJC4 p.Leu22Phe (c.64C>T) is classified Likely benign in DNAJC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-07). AlphaMissense: likely benign (0.0874); Very rare (popmax 0.00343%, sas).

How common is DNAJC4 p.Leu22Phe (c.64C>T) in the general population?

DNAJC4 p.Leu22Phe (c.64C>T) is very rare (popmax 0.00343%, sas) (gnomAD).

What do computational predictors say about DNAJC4 p.Leu22Phe (c.64C>T)?

AlphaMissense predicts likely benign (score 0.0874) — an in-silico prediction, not a clinical call.

DNAJC4 p.Leu22Phe

c.64C>T · VCV4013689

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0874 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00343%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0874	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -7.84	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 0.32	GERP -2.2, phastCons 0.19
Regional constraint	o/e 1.07	unconstrained · MANE · 3,326 bp · p 0.24 · regional, not allelic
Overall
CADD	8.516	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00343% South Asian · 3/87,434 alleles

Filtering AF 0.000911% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000453%

Overall 0.000211% 3/1,422,244 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: DNAJC4
Protein: p.Leu22Phe
Coding: c.64C>T
MANE Select: NM_005528
Type: single nucleotide variant
Location: chr11:64230918 (GRCh38)
Gene constraint: LOEUF 1.444 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.83

Full DNAJC4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJC4 p.Ala200Asp Uncertain significance ★ ⚠ same type
DNAJC4 p.Ala204Pro Uncertain significance ★ ⚠ same type
DNAJC4 p.Ala26Thr Uncertain significance ★ ⚠ same type
DNAJC4 p.Arg100Cys Uncertain significance ★ ⚠ same type
DNAJC4 p.Arg100His Uncertain significance ★ ⚠ same type
DNAJC4 p.Arg109Pro Uncertain significance ★ ⚠ same type
DNAJC4 p.Arg15Gly Uncertain significance ★ ⚠ same type
DNAJC4 p.Arg201Trp 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/dnajc4-p-leu22phe (accessed [today's date]).

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