Is FOXC2 p.Ala201Val (c.602C>T) pathogenic?

FOXC2 p.Ala201Val (c.602C>T) is classified Conflicting classifications of pathogenicity in FOXC2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-11-23). AlphaMissense: likely benign (0.0873); Rare (popmax 0.121%, eas); Associated with Inborn genetic diseases.

What condition is associated with FOXC2 p.Ala201Val (c.602C>T)?

FOXC2 p.Ala201Val (c.602C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FOXC2 p.Ala201Val (c.602C>T) in the general population?

FOXC2 p.Ala201Val (c.602C>T) is rare (popmax 0.121%, eas) (gnomAD).

What do computational predictors say about FOXC2 p.Ala201Val (c.602C>T)?

AlphaMissense predicts likely benign (score 0.0873) — an in-silico prediction, not a clinical call.

FOXC2 p.Ala201Val

c.602C>T · rs764469563 · VCV2721802

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0873 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.121%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0873	likely benign
REVEL	0.257	benign-leaning
SaProt	LLR -7.50	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP -3.1, phastCons 1
Regional constraint	o/e 1.27	unconstrained · MANE · 1,003 bp · p 1.1e-09 · regional, not allelic
Overall
CADD	21.0	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 0.121% East Asian · 54/44,648 alleles

Filtering AF 0.0951% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0859%

Overall 0.00371% 58/1,563,748 alleles · rare exomes 54/1,411,514 · genomes 4/152,234 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.121%	827
Remaining individualsnot grpmax-eligible	0.00331%	30,195
Finnishnot grpmax-eligible	0.00191%	52,332
European (non-Finnish)	8.56e-05%	1,168,164

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: FOXC2
Protein: p.Ala201Val
Coding: c.602C>T
MANE Select: NM_005251
dbSNP: rs764469563
Type: single nucleotide variant
Location: chr16:86567937 (GRCh38)
Gene constraint: LOEUF 1.807 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 56.45 · 8 PDB
Residue 201: the 'disordered' region

Full FOXC2 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

FOXC2 p.Ala194Ser Uncertain significance ★★ ⚠ same condition
FOXC2 p.Ala326Gly Uncertain significance ★★ ⚠ same condition
FOXC2 p.Gly295Ser Uncertain significance ★★ ⚠ same condition
FOXC2 p.Gly314Asp Uncertain significance ★★ ⚠ same condition
FOXC2 p.Gly467Glu Uncertain significance ★★ ⚠ same condition
FOXC2 p.Ile120Val Uncertain significance ★★ ⚠ same condition
FOXC2 p.Met453Ile Uncertain significance ★★ ⚠ same condition
FOXC2 p.Pro107Ala 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/foxc2-p-ala201val (accessed [today's date]).

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