Is KRT85 p.Pro64Thr (c.190C>A) pathogenic?

KRT85 p.Pro64Thr (c.190C>A) is classified Conflicting classifications of pathogenicity in KRT85 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-11-03). AlphaMissense: likely benign (0.193); Rare (popmax 0.25%, mid).

How common is KRT85 p.Pro64Thr (c.190C>A) in the general population?

KRT85 p.Pro64Thr (c.190C>A) is rare (popmax 0.25%, mid) (gnomAD).

What do computational predictors say about KRT85 p.Pro64Thr (c.190C>A)?

AlphaMissense predicts likely benign (score 0.193) — an in-silico prediction, not a clinical call.

KRT85 p.Pro64Thr

c.190C>A · rs200758226 · VCV2322645

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.193 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.25%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.193	likely benign
REVEL	0.305	indeterminate
SaProt	LLR -6.74	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 5.8	GERP 1.8, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 305 bp · p 0.17 · regional, not allelic
Overall
CADD	22.3	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 0.25% Middle Eastern · 15/6,010 alleles

Filtering AF 0.154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.124%

Overall 0.0237% 382/1,613,478 alleles · rare exomes 351/1,461,118 · genomes 31/152,360 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.464%	216
Middle Easterngrpmax	0.25%	401
Remaining individualsnot grpmax-eligible	0.0496%	2,015
European (non-Finnish)	0.0153%	6,517
Admixed American	0.015%	6,665
South Asian	0.00879%	11,377
African / African-American	0.00133%	75,060

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: KRT85
Protein: p.Pro64Thr
Coding: c.190C>A
MANE Select: NM_002283
dbSNP: rs200758226
Type: single nucleotide variant
Location: chr12:52367216 (GRCh38)
Gene constraint: LOEUF 0.89 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.09
Residue 64: 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-pro64thr (accessed [today's date]).

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