Is KRT85 p.Phe71Ser (c.212T>C) pathogenic?

KRT85 p.Phe71Ser (c.212T>C) is classified Conflicting classifications of pathogenicity in KRT85 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-10-21). AlphaMissense: likely benign (0.2875); Rare (popmax 0.574%, afr).

How common is KRT85 p.Phe71Ser (c.212T>C) in the general population?

KRT85 p.Phe71Ser (c.212T>C) is rare (popmax 0.574%, afr) (gnomAD).

What do computational predictors say about KRT85 p.Phe71Ser (c.212T>C)?

AlphaMissense predicts likely benign (score 0.2875) — an in-silico prediction, not a clinical call.

KRT85 p.Phe71Ser

c.212T>C · rs139493548 · VCV2044082

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2875 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.574%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2875	likely benign
REVEL	0.371	indeterminate
SaProt	LLR -6.54	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 0.95, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 305 bp · p 0.17 · regional, not allelic
Overall
CADD	18.24	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 0.574% African / African-American · 431/75,034 alleles

Filtering AF 0.53% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.512%

Overall 0.0311% 502/1,613,810 alleles · rare exomes 235/1,461,504 · genomes 267/152,306 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.574%	174
Admixed American	0.0533%	1,875
Remaining individualsnot grpmax-eligible	0.0384%	2,604
Middle Eastern	0.0168%	5,936
European (non-Finnish)	0.00119%	84,282

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: KRT85
Protein: p.Phe71Ser
Coding: c.212T>C
MANE Select: NM_002283
dbSNP: rs139493548
Type: single nucleotide variant
Location: chr12:52367194 (GRCh38)
Gene constraint: LOEUF 0.89 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.09
Residue 71: the 'head' region

Full KRT85 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KRT85 p.Arg142His Uncertain significance ★★ ⚠ same type
KRT85 p.Arg315His Uncertain significance ★★ ⚠ same type
KRT85 p.Arg465His Uncertain significance ★★ ⚠ same type
KRT85 p.Asn115Lys Uncertain significance ★★ ⚠ same type
KRT85 p.Glu352Lys Uncertain significance ★★ ⚠ same type
KRT85 p.Gly390Ser Uncertain significance ★★ ⚠ same type
KRT85 p.Gly89Arg Uncertain significance ★★ ⚠ same type
KRT85 c.1078-17G>A Benign/Likely benign ★★ 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/krt85-p-phe71ser (accessed [today's date]).

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