Is KRT17 p.Ser71Arg (c.213C>A) pathogenic?

KRT17 p.Ser71Arg (c.213C>A) is classified Uncertain significance in KRT17 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-24). AlphaMissense: likely pathogenic (0.5724); Ultra-rare (popmax 0.0399%, nfe); Associated with Inborn genetic diseases.

What condition is associated with KRT17 p.Ser71Arg (c.213C>A)?

KRT17 p.Ser71Arg (c.213C>A) is associated with Inborn genetic diseases (ClinVar).

How common is KRT17 p.Ser71Arg (c.213C>A) in the general population?

KRT17 p.Ser71Arg (c.213C>A) is ultra-rare (popmax 0.0399%, nfe) (gnomAD).

What do computational predictors say about KRT17 p.Ser71Arg (c.213C>A)?

AlphaMissense predicts likely pathogenic (score 0.5724) — an in-silico prediction, not a clinical call.

KRT17 p.Ser71Arg

c.213C>A · rs371521134 · VCV2361893

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5724 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0399%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5724	likely pathogenic
REVEL	0.198	benign-leaning
SaProt	LLR -10.33	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.48	GERP 1.9, phastCons 0.93
Regional constraint	o/e 0.93	unconstrained · MANE · 4,912 bp · p 0.082 · regional, not allelic
Overall
CADD	16.89	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 0.0399% European (non-Finnish) · 471/1,179,980 alleles

Filtering AF 0.0369% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0357%

Overall 0.0301% 485/1,612,104 alleles · ultra-rare exomes 470/1,459,904 · genomes 15/152,200 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0399%	2,505
Remaining individualsnot grpmax-eligible	0.00963%	10,385
African / African-American	0.00668%	14,972
Finnishnot grpmax-eligible	0.00313%	31,978
Admixed American	0.00167%	60,010

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: KRT17
Protein: p.Ser71Arg
Coding: c.213C>A
MANE Select: NM_000422
dbSNP: rs371521134
Type: single nucleotide variant
Location: chr17:41624297 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.28
Residue 71: the 'head' region

Full KRT17 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

KRT17 p.Arg406Cys Uncertain significance ★★ ⚠ same condition
KRT17 p.Ala178Pro Uncertain significance ★ ⚠ same condition
KRT17 p.Ala354Asp Uncertain significance ★ ⚠ same condition
KRT17 p.Arg251Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
KRT17 p.Arg257His Uncertain significance ★ ⚠ same condition
KRT17 p.Asp118Glu Uncertain significance ★ ⚠ same condition
KRT17 p.Asp195Glu Uncertain significance ★ ⚠ same condition
KRT17 p.Gln315Arg 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/krt17-p-ser71arg (accessed [today's date]).

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