Is FOXC2 p.Ser36= (c.108C>T) pathogenic?

FOXC2 p.Ser36= (c.108C>T) is classified Benign/Likely benign in FOXC2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-04-01). Low-frequency (popmax 2.57%, mid).

How common is FOXC2 p.Ser36= (c.108C>T) in the general population?

FOXC2 p.Ser36= (c.108C>T) is low-frequency (popmax 2.57%, mid) (gnomAD).

FOXC2 p.Ser36=

c.108C>T · rs138318843 · VCV259691

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.57%, mid)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.79	GERP -4.3, phastCons 1
Overall
CADD	12.09	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.57% Middle Eastern · 156/6,062 alleles

Filtering AF 2.24% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.12%

Overall 0.792% 12,771/1,613,278 alleles · low-frequency exomes 11,796/1,460,988 · genomes 975/152,290 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	2.57%	39
Amishnot grpmax-eligible	1.64%	61
European (non-Finnish)	0.944%	106
Remaining individualsnot grpmax-eligible	0.749%	134
Admixed American	0.617%	162
Finnishnot grpmax-eligible	0.245%	409
South Asian	0.242%	414
African / African-American	0.241%	415
Ashkenazi Jewishnot grpmax-eligible	0.22%	455

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.Ser36=
Coding: c.108C>T
MANE Select: NM_005251
dbSNP: rs138318843
Type: single nucleotide variant
Location: chr16:86567443 (GRCh38)

Full FOXC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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-ser36 (accessed [today's date]).

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