Is FAT1 p.Pro4312= (c.12936C>T) pathogenic?

FAT1 p.Pro4312= (c.12936C>T) is classified Benign/Likely benign in FAT1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). Common (popmax 17.8%, eas) — too common for a highly-penetrant pathogenic allele.

FAT1 p.Pro4312=

Q: How common is FAT1 p.Pro4312= (c.12936C>T) in the general population?

FAT1 p.Pro4312= (c.12936C>T) is common (popmax 17.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.12936C>T · rs3822060 · VCV1291302

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 17.8%, eas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.194	benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -9.7	GERP -3.8
Overall
CADD	0.012	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 17.8% East Asian · 7,961/44,834 alleles

Filtering AF 17.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 17.3%

Overall 3.97% 63,972/1,612,564 alleles · common exomes 58,082/1,460,356 · genomes 5,890/152,208 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	17.8%	6
Admixed American	12.9%	8
Finnishnot grpmax-eligible	9.24%	11
Amishnot grpmax-eligible	4.4%	23
Remaining individualsnot grpmax-eligible	3.98%	25
European (non-Finnish)	3.2%	31
South Asian	1.48%	68
Ashkenazi Jewishnot grpmax-eligible	0.725%	138
African / African-American	0.704%	142
Middle Eastern	0.612%	163

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: FAT1
Protein: p.Pro4312=
Coding: c.12936C>T
MANE Select: NM_005245
dbSNP: rs3822060
Type: single nucleotide variant
Location: chr4:186596604 (GRCh38)
Gene constraint: LOEUF 0.571 · pLI <0.01 (gnomAD)
Residue 4312: the 'disordered' region

Full FAT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FAT1 p.Ala1663Thr Uncertain significance ★★ same type
FAT1 p.Ala1762Val Uncertain significance ★★ ⚠ same type
FAT1 p.Ala1862Ser Uncertain significance ★★ ⚠ same type
FAT1 p.Ala2046Thr Uncertain significance ★★ ⚠ same type
FAT1 p.Ala2456Thr Uncertain significance ★★ ⚠ same type
FAT1 p.Ala2502Asp Uncertain significance ★★ ⚠ same type
FAT1 p.Ala3007Val Uncertain significance ★★ same type
FAT1 p.Ala3437Thr Uncertain significance ★★ ⚠ same type

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/fat1-p-pro4312 (accessed [today's date]).

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