Is KRT1 p.Arg86Ser (c.256C>A) pathogenic?

KRT1 p.Arg86Ser (c.256C>A) is classified Benign/Likely benign in KRT1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-08-04). AlphaMissense: likely benign (0.2301); Rare (popmax 0.801%, afr).

How common is KRT1 p.Arg86Ser (c.256C>A) in the general population?

KRT1 p.Arg86Ser (c.256C>A) is rare (popmax 0.801%, afr) (gnomAD).

What do computational predictors say about KRT1 p.Arg86Ser (c.256C>A)?

AlphaMissense predicts likely benign (score 0.2301) — an in-silico prediction, not a clinical call.

KRT1 p.Arg86Ser

c.256C>A · rs145256530 · VCV784241

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2301 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.801%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2301	likely benign
REVEL	0.149	moderately benign-leaning
SaProt	LLR -5.47	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 0.59	GERP -2.6
Regional constraint	o/e 0.96	unconstrained · MANE · 5,152 bp · p 0.25 · regional, not allelic
Overall
CADD	2.841	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 0.801% African / African-American · 584/72,888 alleles

Filtering AF 0.747% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.726%

Overall 0.0448% 698/1,556,666 alleles · rare exomes 334/1,405,350 · genomes 364/151,316 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.801%	125
Admixed American	0.104%	964
Middle Eastern	0.0834%	1,199
Remaining individualsnot grpmax-eligible	0.0729%	1,372
South Asian	0.00117%	85,128
European (non-Finnish)	0.000956%	104,571

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: KRT1
Protein: p.Arg86Ser
Coding: c.256C>A
MANE Select: NM_006121
dbSNP: rs145256530
Type: single nucleotide variant
Location: chr12:52680093 (GRCh38)
Gene constraint: LOEUF 0.7 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.62 · 3 PDB
Residue 86: the 'head' region

Full KRT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KRT1 p.Arg86His Uncertain significance ★★ ⚠ same residue
KRT1 p.Arg86Cys Uncertain significance ★ ⚠ same residue
KRT1 c.1255-1G>T Pathogenic ★★ same type
KRT1 c.591+1G>C Pathogenic ★★ same type
KRT1 p.Asn188Lys Pathogenic ★★ same type
KRT1 p.Asn188Ser Pathogenic/Likely pathogenic ★★ same type
KRT1 p.Ile195Asn Pathogenic/Likely pathogenic ★★ same type
KRT1 p.Ile479Thr Pathogenic/Likely pathogenic ★★ 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/krt1-p-arg86ser (accessed [today's date]).

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