Is KRT6A p.Ser29Arg (c.87C>A) pathogenic?

KRT6A p.Ser29Arg (c.87C>A) is classified Uncertain significance in KRT6A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-13). AlphaMissense: ambiguous (0.4572); Rare (popmax 0.102%, mid); Associated with Inborn genetic diseases.

What condition is associated with KRT6A p.Ser29Arg (c.87C>A)?

KRT6A p.Ser29Arg (c.87C>A) is associated with Inborn genetic diseases (ClinVar).

How common is KRT6A p.Ser29Arg (c.87C>A) in the general population?

KRT6A p.Ser29Arg (c.87C>A) is rare (popmax 0.102%, mid) (gnomAD).

What do computational predictors say about KRT6A p.Ser29Arg (c.87C>A)?

AlphaMissense predicts ambiguous (score 0.4572) — an in-silico prediction, not a clinical call.

KRT6A p.Ser29Arg

c.87C>A · VCV3536092

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4572 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.102%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4572	ambiguous
REVEL	0.242	benign-leaning
SaProt	LLR -8.07	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.3	GERP -0.22
Regional constraint	o/e 1.17	unconstrained · MANE · 129 bp · p 0.19 · regional, not allelic
Overall
CADD	16.37	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 0.102% Middle Eastern · 6/5,896 alleles

Filtering AF 0.0443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0302%

Overall 0.00508% 82/1,613,838 alleles · rare exomes 75/1,461,636 · genomes 7/152,202 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.102%	983
Admixed American	0.0233%	4,286
South Asian	0.00769%	13,009
Remaining individualsnot grpmax-eligible	0.0064%	15,615
European (non-Finnish)	0.00424%	23,601
African / African-American	0.00133%	74,926

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: KRT6A
Protein: p.Ser29Arg
Coding: c.87C>A
MANE Select: NM_005554
Type: single nucleotide variant
Location: chr12:52493102 (GRCh38)
Gene constraint: LOEUF 0.755 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.16 · 1 PDB
Residue 29: the 'head' region

Full KRT6A 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

KRT6A p.Ala403Thr Uncertain significance ★★ ⚠ same condition
KRT6A p.Arg16Trp Uncertain significance ★★ ⚠ same condition
KRT6A p.Arg240Gly Uncertain significance ★★ same condition
KRT6A p.Gly202Ser Uncertain significance ★★ ⚠ same condition
KRT6A p.Gly510Asp Uncertain significance ★★ same condition
KRT6A p.Lys400Gln Uncertain significance ★★ ⚠ same condition
KRT6A p.Val282Phe Uncertain significance ★★ ⚠ same condition
KRT6A p.Val481Ile 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/krt6a-p-ser29arg (accessed [today's date]).

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