Is KRT12 p.Asn206Ser (c.617A>G) pathogenic?

KRT12 p.Asn206Ser (c.617A>G) is classified Conflicting classifications of pathogenicity in KRT12 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-21). AlphaMissense: likely benign (0.2673); Low-frequency (popmax 2.8%, mid); Associated with Inborn genetic diseases.

What condition is associated with KRT12 p.Asn206Ser (c.617A>G)?

KRT12 p.Asn206Ser (c.617A>G) is associated with Inborn genetic diseases (ClinVar).

How common is KRT12 p.Asn206Ser (c.617A>G) in the general population?

KRT12 p.Asn206Ser (c.617A>G) is low-frequency (popmax 2.8%, mid) (gnomAD).

What do computational predictors say about KRT12 p.Asn206Ser (c.617A>G)?

AlphaMissense predicts likely benign (score 0.2673) — an in-silico prediction, not a clinical call.

KRT12 p.Asn206Ser

c.617A>G · rs147584242 · VCV2056565

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2673 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.8%, mid)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2673	likely benign
REVEL	0.65	pathogenic-leaning
SaProt	LLR -11.03	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 5,522 bp · p 0.13 · regional, not allelic
Overall
CADD	23.0	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 2.8% Middle Eastern · 170/6,062 alleles

Filtering AF 2.46% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.33%

Overall 0.259% 4,182/1,614,146 alleles · low-frequency exomes 3,903/1,461,828 · genomes 279/152,318 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	2.8%	36
Ashkenazi Jewishnot grpmax-eligible	0.503%	199
Remaining individualsnot grpmax-eligible	0.312%	321
Admixed American	0.29%	345
European (non-Finnish)	0.277%	361
South Asian	0.117%	851
Finnishnot grpmax-eligible	0.102%	985
African / African-American	0.0666%	1,501
East Asian	0.00446%	22,438

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: KRT12
Protein: p.Asn206Ser
Coding: c.617A>G
MANE Select: NM_000223
dbSNP: rs147584242
Type: single nucleotide variant
Location: chr17:40866188 (GRCh38)
Gene constraint: LOEUF 0.979 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.57
Residue 206: the if rod domain; the 'coil 1b' region

Full KRT12 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

KRT12 p.Met129Val Pathogenic/Likely pathogenic ★★ same condition
KRT12 p.Asp213Tyr Uncertain significance ★★ ⚠ same condition
KRT12 p.Gln486Glu Uncertain significance ★★ ⚠ same condition
KRT12 p.Ile195Phe Uncertain significance ★★ ⚠ same condition
KRT12 p.Val228Ile Uncertain significance ★★ ⚠ same condition
KRT12 p.Ala149Val Uncertain significance ★ ⚠ same condition
KRT12 p.Ala171Thr Uncertain significance ★ ⚠ same condition
KRT12 p.Ala207Val 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/krt12-p-asn206ser (accessed [today's date]).

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