Is KRT2 p.Ala85Ser (c.253G>T) pathogenic?

KRT2 p.Ala85Ser (c.253G>T) is classified Likely benign in KRT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-14). AlphaMissense: likely benign (0.067); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with KRT2 p.Ala85Ser (c.253G>T)?

KRT2 p.Ala85Ser (c.253G>T) is associated with Inborn genetic diseases (ClinVar).

How common is KRT2 p.Ala85Ser (c.253G>T) in the general population?

KRT2 p.Ala85Ser (c.253G>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about KRT2 p.Ala85Ser (c.253G>T)?

AlphaMissense predicts likely benign (score 0.067) — an in-silico prediction, not a clinical call.

KRT2 p.Ala85Ser

c.253G>T · VCV3865430

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.067 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.067	likely benign
REVEL	0.16	moderately benign-leaning
SaProt	LLR -5.55	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.5	GERP -4.3
Regional constraint	o/e 1.08	unconstrained · MANE · 7,120 bp · p 0.023 · regional, not allelic
Overall
CADD	0.977	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 0.0011% South Asian · 1/90,830 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000435% 7/1,609,870 alleles · very rare exomes 7/1,457,760 · genomes 0/152,110 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0136%	7,359
South Asiangrpmax	0.0011%	90,830
European (non-Finnish)	0.00017%	588,776

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: KRT2
Protein: p.Ala85Ser
Coding: c.253G>T
MANE Select: NM_000423
Type: single nucleotide variant
Location: chr12:52651890 (GRCh38)
Gene constraint: LOEUF 1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.38
Residue 85: the 'head' region

Full KRT2 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

KRT2 p.Ala85Thr Uncertain significance ★ ⚠ same residue
KRT2 p.Arg544Gln Uncertain significance ★★ ⚠ same condition
KRT2 p.Asn498Ile Uncertain significance ★★ ⚠ same condition
KRT2 p.Val402Met Likely benign ★★ same condition
KRT2 p.Ala190Ser Uncertain significance ★ ⚠ same condition
KRT2 p.Ala278Thr Uncertain significance ★ ⚠ same condition
KRT2 p.Ala350Thr Uncertain significance ★ ⚠ same condition
KRT2 p.Ala369Ser 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/krt2-p-ala85ser (accessed [today's date]).

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