Is KRT85 p.Arg142Cys (c.424C>T) pathogenic?

KRT85 p.Arg142Cys (c.424C>T) is classified Uncertain significance in KRT85 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-30). AlphaMissense: ambiguous (0.5207); Ultra-rare (popmax 0.0144%, nfe).

How common is KRT85 p.Arg142Cys (c.424C>T) in the general population?

KRT85 p.Arg142Cys (c.424C>T) is ultra-rare (popmax 0.0144%, nfe) (gnomAD).

What do computational predictors say about KRT85 p.Arg142Cys (c.424C>T)?

AlphaMissense predicts ambiguous (score 0.5207) — an in-silico prediction, not a clinical call.

KRT85 p.Arg142Cys

c.424C>T · rs148274330 · VCV2264090

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5207 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0144%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5207	ambiguous
REVEL	0.913	moderately pathogenic-leaning
SaProt	LLR -11.33	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 6,136 bp · p 0.65 · regional, not allelic
Overall
CADD	31.0	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 0.0144% European (non-Finnish) · 170/1,180,022 alleles

Filtering AF 0.0126% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0119%

Overall 0.0118% 190/1,614,066 alleles · ultra-rare exomes 178/1,461,698 · genomes 12/152,368 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0144%	6,941
South Asian	0.0132%	7,591
Admixed American	0.00333%	30,014
Remaining individualsnot grpmax-eligible	0.0032%	31,245
African / African-American	0.00266%	37,534
East Asian	0.00223%	44,880
Finnishnot grpmax-eligible	0.00156%	63,938

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.Arg142Cys
Coding: c.424C>T
MANE Select: NM_002283
dbSNP: rs148274330
Type: single nucleotide variant
Location: chr12:52365167 (GRCh38)
Gene constraint: LOEUF 0.89 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.09
Residue 142: 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 residue
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-arg142cys (accessed [today's date]).

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