Is KRT85 p.Phe157Ser (c.470T>C) pathogenic?

KRT85 p.Phe157Ser (c.470T>C) is classified Uncertain significance in KRT85 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely pathogenic (0.9172); Very rare (popmax 0.00267%, afr).

How common is KRT85 p.Phe157Ser (c.470T>C) in the general population?

KRT85 p.Phe157Ser (c.470T>C) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about KRT85 p.Phe157Ser (c.470T>C)?

AlphaMissense predicts likely pathogenic (score 0.9172) — an in-silico prediction, not a clinical call.

KRT85 p.Phe157Ser

c.470T>C · rs771828733 · VCV3116774

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9172 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9172	likely pathogenic · top 10% in KRT85
REVEL	0.604	indeterminate
SaProt	LLR -8.34	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 0.99, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 6,136 bp · p 0.65 · regional, not allelic
Overall
CADD	26.7	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 0.00267% African / African-American · 2/74,946 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000496% 8/1,614,104 alleles · very rare exomes 6/1,461,868 · genomes 2/152,236 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,473
Admixed American	0.00167%	60,012
European (non-Finnish)	0.000424%	236,011

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.Phe157Ser
Coding: c.470T>C
MANE Select: NM_002283
dbSNP: rs771828733
Type: single nucleotide variant
Location: chr12:52365121 (GRCh38)
Gene constraint: LOEUF 0.89 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.09
Residue 157: the if rod domain; the 'coil 1a' 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-phe157ser (accessed [today's date]).

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