Is KRT6B p.Arg9Ser (c.27G>C) pathogenic?

KRT6B p.Arg9Ser (c.27G>C) is classified Uncertain significance in KRT6B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-29). AlphaMissense: likely benign (0.2632); Ultra-rare (popmax 0.07%, amr); Associated with Inborn genetic diseases.

What condition is associated with KRT6B p.Arg9Ser (c.27G>C)?

KRT6B p.Arg9Ser (c.27G>C) is associated with Inborn genetic diseases (ClinVar).

How common is KRT6B p.Arg9Ser (c.27G>C) in the general population?

KRT6B p.Arg9Ser (c.27G>C) is ultra-rare (popmax 0.07%, amr) (gnomAD).

What do computational predictors say about KRT6B p.Arg9Ser (c.27G>C)?

AlphaMissense predicts likely benign (score 0.2632) — an in-silico prediction, not a clinical call.

KRT6B p.Arg9Ser

c.27G>C · VCV4045066

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2632 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.07%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2632	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	LLR -6.32	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 -7.4	GERP 0.54
Regional constraint	o/e 0.80	unconstrained · MANE · 214 bp · p 0.048 · regional, not allelic
Overall
CADD	16.03	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 0.07% Admixed American · 42/59,996 alleles

Filtering AF 0.0532% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0473%

Overall 0.00266% 43/1,613,938 alleles · ultra-rare exomes 15/1,461,850 · genomes 28/152,088 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.07%	1,428
European (non-Finnish)	8.47e-05%	1,180,020

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.Arg9Ser
Coding: c.27G>C
MANE Select: NM_005555
Type: single nucleotide variant
Location: chr12:52452052 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.76
Residue 9: the 'disordered' region; 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-arg9ser (accessed [today's date]).

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