Is KRT6C p.Phe100Val (c.298T>G) pathogenic?

KRT6C p.Phe100Val (c.298T>G) is classified Uncertain significance in KRT6C (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-23). AlphaMissense: likely benign (0.1524); No allele count reported in gnomAD v4.1 (AN 1,371,206); Associated with Inborn genetic diseases.

What condition is associated with KRT6C p.Phe100Val (c.298T>G)?

KRT6C p.Phe100Val (c.298T>G) is associated with Inborn genetic diseases (ClinVar).

How common is KRT6C p.Phe100Val (c.298T>G) in the general population?

KRT6C p.Phe100Val (c.298T>G) is no allele count reported in gnomAD v4.1 (AN 1,371,206) (gnomAD).

What do computational predictors say about KRT6C p.Phe100Val (c.298T>G)?

AlphaMissense predicts likely benign (score 0.1524) — an in-silico prediction, not a clinical call.

KRT6C p.Phe100Val

c.298T>G · rs1349369885 · VCV2477584

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1524 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,371,206)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1524	likely benign
REVEL	0.323	indeterminate
SaProt	LLR -8.06	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.1	GERP 1.8
Regional constraint	o/e 0.28	constrained · MANE · 1,340 bp · p 3.8e-24 · regional, not allelic
Overall
CADD	14.17	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,371,206). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: KRT6C
Protein: p.Phe100Val
Coding: c.298T>G
MANE Select: NM_173086
dbSNP: rs1349369885
Type: single nucleotide variant
Location: chr12:52473440 (GRCh38)
Gene constraint: LOEUF 1.34 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.63
Residue 100: the 'head' region

Full KRT6C 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

KRT6C p.Phe100Ile Uncertain significance ★ ⚠ same residue
KRT6C p.Arg260Cys Uncertain significance ★★ ⚠ same condition
KRT6C p.Arg349Trp Uncertain significance ★★ ⚠ same condition
KRT6C p.Arg466Cys Uncertain significance ★★ ⚠ same condition
KRT6C p.Asp331His Uncertain significance ★★ ⚠ same condition
KRT6C p.Glu479Lys Uncertain significance ★★ same condition
KRT6C p.Gly504Ser Uncertain significance ★★ ⚠ same condition
KRT6C p.Gly525Ser 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/krt6c-p-phe100val (accessed [today's date]).

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