Is DNAJC27 p.Phe41= (c.123C>T) pathogenic?

DNAJC27 p.Phe41= (c.123C>T) is classified Likely benign in DNAJC27 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-25). Common (popmax 37.9%, afr) — too common for a highly-penetrant pathogenic allele.

DNAJC27 p.Phe41=

Q: How common is DNAJC27 p.Phe41= (c.123C>T) in the general population?

DNAJC27 p.Phe41= (c.123C>T) is common (popmax 37.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.123C>T · VCV3504019

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 37.9%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -4.4, phastCons 1
Overall
CADD	8.343	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 37.9% African / African-American · 28,275/74,666 alleles

Filtering AF 37.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 37.3%

Overall 5.47% 88,251/1,611,958 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	37.9%	3
Amishnot grpmax-eligible	10.1%	10
Middle Eastern	7.02%	14
South Asian	7.01%	14
Remaining individualsnot grpmax-eligible	6.08%	16
Admixed American	4.47%	22
Ashkenazi Jewishnot grpmax-eligible	4.35%	23
European (non-Finnish)	3.74%	27
Finnishnot grpmax-eligible	1.92%	52
East Asian	0.0513%	1,951

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: DNAJC27
Protein: p.Phe41=
Coding: c.123C>T
MANE Select: NM_016544
Type: single nucleotide variant
Location: chr2:24967258 (GRCh38)
Gene constraint: LOEUF 0.799 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 90.75 · 1 PDB

Full DNAJC27 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DNAJC27 p.Ala106Val Uncertain significance ★ ⚠ same type
DNAJC27 p.Ala236Val Uncertain significance ★ ⚠ same type
DNAJC27 p.Ala264Val Uncertain significance ★ ⚠ same type
DNAJC27 p.Ala73Val Uncertain significance ★ ⚠ same type
DNAJC27 p.Arg142His Uncertain significance ★ ⚠ same type
DNAJC27 p.Arg150Cys Uncertain significance ★ ⚠ same type
DNAJC27 p.Arg192His Uncertain significance ★ ⚠ same type
DNAJC27 p.Arg210Cys 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/dnajc27-p-phe41 (accessed [today's date]).

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