Is KRT6A p.Ser5Phe (c.14C>T) pathogenic?

KRT6A p.Ser5Phe (c.14C>T) is classified Likely benign in KRT6A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-02-05). AlphaMissense: likely benign (0.2259); Rare (popmax 0.229%, sas); Associated with KRT6A-related disorder.

What condition is associated with KRT6A p.Ser5Phe (c.14C>T)?

KRT6A p.Ser5Phe (c.14C>T) is associated with KRT6A-related disorder (ClinVar).

How common is KRT6A p.Ser5Phe (c.14C>T) in the general population?

KRT6A p.Ser5Phe (c.14C>T) is rare (popmax 0.229%, sas) (gnomAD).

What do computational predictors say about KRT6A p.Ser5Phe (c.14C>T)?

AlphaMissense predicts likely benign (score 0.2259) — an in-silico prediction, not a clinical call.

KRT6A p.Ser5Phe

c.14C>T · rs563614469 · VCV3041915

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2259 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.229%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

KRT6A-related disorder

Computational evidence

Protein change
AlphaMissense	0.2259	likely benign
REVEL	0.124	moderately benign-leaning
SaProt	LLR -8.23	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 -0.14	GERP 1.4, phastCons 0.001
Regional constraint	o/e 1.17	unconstrained · MANE · 129 bp · p 0.19 · regional, not allelic
Overall
CADD	23.6	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 0.229% South Asian · 209/91,076 alleles

Filtering AF 0.204% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.194%

Overall 0.0136% 219/1,614,156 alleles · rare exomes 207/1,461,828 · genomes 12/152,328 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.229%	436
Middle Eastern	0.033%	3,029
Remaining individualsnot grpmax-eligible	0.0128%	7,812

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.Ser5Phe
Coding: c.14C>T
MANE Select: NM_005554
dbSNP: rs563614469
Type: single nucleotide variant
Location: chr12:52493175 (GRCh38)
Gene constraint: LOEUF 0.755 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.16 · 1 PDB
Residue 5: the 'disordered' region; the 'head' region

Full KRT6A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

KRT6A-related disorder

Similar variants

KRT6A p.Arg164Cys Pathogenic/Likely pathogenic ★★ same condition
KRT6A p.Asn171Lys Pathogenic ★★ same condition
KRT6A p.Ala106= Likely benign same condition
KRT6A p.Ala442= Likely benign same condition
KRT6A p.Arg15His Likely benign ⚠ same condition
KRT6A p.Arg443Gln Benign ⚠ same condition
KRT6A p.Gly95= Likely benign same condition
KRT6A p.Leu112= Likely benign 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-ser5phe (accessed [today's date]).

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