Is KRT74 p.Pro24Arg (c.71C>G) pathogenic?

KRT74 p.Pro24Arg (c.71C>G) is classified Likely benign in KRT74 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-24). AlphaMissense: likely benign (0.1018); Rare (popmax 0.157%, amr).

How common is KRT74 p.Pro24Arg (c.71C>G) in the general population?

KRT74 p.Pro24Arg (c.71C>G) is rare (popmax 0.157%, amr) (gnomAD).

What do computational predictors say about KRT74 p.Pro24Arg (c.71C>G)?

AlphaMissense predicts likely benign (score 0.1018) — an in-silico prediction, not a clinical call.

KRT74 p.Pro24Arg

c.71C>G · rs777863467 · VCV1093378

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1018 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.157%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1018	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -6.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2	phastCons 0.95
Regional constraint	o/e 1.07	unconstrained · MANE · 6,805 bp · p 0.074 · regional, not allelic
Overall
CADD	14.24	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 0.157% Admixed American · 94/60,032 alleles

Filtering AF 0.131% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.121%

Overall 0.00607% 98/1,614,144 alleles · rare exomes 84/1,461,796 · genomes 14/152,348 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.157%	639
Remaining individualsnot grpmax-eligible	0.0048%	20,836
European (non-Finnish)	8.47e-05%	1,180,040

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: KRT74
Protein: p.Pro24Arg
Coding: c.71C>G
MANE Select: NM_175053
dbSNP: rs777863467
Type: single nucleotide variant
Location: chr12:52573707 (GRCh38)
Gene constraint: LOEUF 1.278 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.11
Residue 24: the 'head' region

Full KRT74 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KRT74 p.Ala410Thr Uncertain significance ★★ ⚠ same type
KRT74 p.Arg141Gln Uncertain significance ★★ ⚠ same type
KRT74 p.Arg346Gln Uncertain significance ★★ ⚠ same type
KRT74 p.Arg69Trp Uncertain significance ★★ ⚠ same type
KRT74 p.Asp221Val Uncertain significance ★★ ⚠ same type
KRT74 p.Gln426Arg Uncertain significance ★★ ⚠ same type
KRT74 p.Ile7Ser Uncertain significance ★★ ⚠ same type
KRT74 p.Leu364His 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/krt74-p-pro24arg (accessed [today's date]).

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