Is KRT6B p.Arg24Ser (c.72G>T) pathogenic?

KRT6B p.Arg24Ser (c.72G>T) is classified Uncertain significance in KRT6B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-03). AlphaMissense: likely benign (0.3225); Ultra-rare (popmax 0.0139%, nfe); Associated with Inborn genetic diseases.

What condition is associated with KRT6B p.Arg24Ser (c.72G>T)?

KRT6B p.Arg24Ser (c.72G>T) is associated with Inborn genetic diseases (ClinVar).

How common is KRT6B p.Arg24Ser (c.72G>T) in the general population?

KRT6B p.Arg24Ser (c.72G>T) is ultra-rare (popmax 0.0139%, nfe) (gnomAD).

What do computational predictors say about KRT6B p.Arg24Ser (c.72G>T)?

AlphaMissense predicts likely benign (score 0.3225) — an in-silico prediction, not a clinical call.

KRT6B p.Arg24Ser

c.72G>T · VCV4045064

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3225 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0139%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3225	likely benign
REVEL	0.196	benign-leaning
SaProt	LLR -4.36	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 -20	GERP -3.8
Regional constraint	o/e 0.80	unconstrained · MANE · 214 bp · p 0.048 · regional, not allelic
Overall
CADD	12.22	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 0.0139% European (non-Finnish) · 164/1,179,898 alleles

Filtering AF 0.0121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0115%

Overall 0.0103% 167/1,613,818 alleles · ultra-rare exomes 163/1,461,498 · genomes 4/152,320 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0139%	7,195
African / African-American	0.00266%	37,525
Admixed American	0.00167%	60,020

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: KRT6B
Protein: p.Arg24Ser
Coding: c.72G>T
MANE Select: NM_005555
Type: single nucleotide variant
Location: chr12:52452007 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.76
Residue 24: the 'head' region

Full KRT6B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KRT6B p.Ala403Val Uncertain significance ★★ ⚠ same condition
KRT6B p.Arg260His Uncertain significance ★★ same condition
KRT6B p.Arg375His Uncertain significance ★★ ⚠ same condition
KRT6B p.Arg386His Uncertain significance ★★ same condition
KRT6B p.Gln208His Uncertain significance ★★ ⚠ same condition
KRT6B p.Gln379Arg Uncertain significance ★★ ⚠ same condition
KRT6B p.Gly103Ser Uncertain significance ★★ ⚠ same condition
KRT6B p.Lys281Gln Uncertain significance ★★ same condition

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/krt6b-p-arg24ser (accessed [today's date]).

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