Is FXR2 p.Pro279= (c.837C>T) pathogenic?

FXR2 p.Pro279= (c.837C>T) is classified Likely benign in FXR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-12-14). Very rare (popmax 0.00892%, eas).

How common is FXR2 p.Pro279= (c.837C>T) in the general population?

FXR2 p.Pro279= (c.837C>T) is very rare (popmax 0.00892%, eas) (gnomAD).

FXR2 p.Pro279=

c.837C>T · rs375991949 · VCV798902

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.5	GERP -4.8
Overall
CADD	2.321	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00892% East Asian · 4/44,850 alleles

Filtering AF 0.00737% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00688%

Overall 0.00704% 113/1,605,740 alleles · very rare exomes 105/1,453,640 · genomes 8/152,100 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,212
European (non-Finnish)	0.00878%	11,384
Admixed American	0.00334%	29,980
African / African-American	0.00268%	37,372
Remaining individualsnot grpmax-eligible	0.00161%	62,182
South Asian	0.0011%	90,910

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: FXR2
Protein: p.Pro279=
Coding: c.837C>T
MANE Select: NM_004860
dbSNP: rs375991949
Type: single nucleotide variant
Location: chr17:7594752 (GRCh38)
Gene constraint: LOEUF 0.321 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.09 · 1 PDB

Full FXR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FXR2 p.Lys651Glu Likely benign ★★ same type
FXR2 p.Pro473= Benign ★★ same type
FXR2 p.Ala166Val Uncertain significance ★ same type
FXR2 p.Ala407Val Uncertain significance ★ ⚠ same type
FXR2 p.Ala466Ser Uncertain significance ★ ⚠ same type
FXR2 p.Ala5Val Uncertain significance ★ ⚠ same type
FXR2 p.Arg327Gln Uncertain significance ★ ⚠ same type
FXR2 p.Arg375His 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/fxr2-p-pro279 (accessed [today's date]).

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