Is FGR p.Asp254= (c.762C>T) pathogenic?

FGR p.Asp254= (c.762C>T) is classified Benign in FGR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2020-02-18). Common (popmax 11.5%, sas) — too common for a highly-penetrant pathogenic allele.

FGR p.Asp254=

Q: How common is FGR p.Asp254= (c.762C>T) in the general population?

FGR p.Asp254= (c.762C>T) is common (popmax 11.5%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.762C>T · rs142998887 · VCV1247746

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 11.5%, sas) — 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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.33	GERP -3.4, phastCons 0.006
Overall
CADD	11.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 11.5% South Asian · 10,310/89,452 alleles

Filtering AF 11.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.3%

Overall 0.687% 11,031/1,604,812 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	11.5%	9
Remaining individualsnot grpmax-eligible	0.741%	135
Middle Eastern	0.347%	288
Ashkenazi Jewishnot grpmax-eligible	0.276%	363
Admixed American	0.0475%	2,106
East Asian	0.0249%	4,019
African / African-American	0.0241%	4,151
European (non-Finnish)	0.00825%	12,123
Finnishnot grpmax-eligible	0.00792%	12,631

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: FGR
Protein: p.Asp254=
Coding: c.762C>T
MANE Select: NM_005248
dbSNP: rs142998887
Type: single nucleotide variant
Location: chr1:27615765 (GRCh38)
Gene constraint: LOEUF 0.556 · pLI 0.50 (gnomAD)
Structure: AlphaFold pLDDT 83.00 · 7 PDB

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

Similar variants

FGR c.533-8C>G Benign ★★ same type
FGR p.Ser122= Benign ★★ same type
FGR p.Ala30Thr Uncertain significance ★ ⚠ same type
FGR p.Ala395Thr Uncertain significance ★ ⚠ same type
FGR p.Ala60Thr Uncertain significance ★ ⚠ same type
FGR p.Ala60Val Uncertain significance ★ ⚠ same type
FGR p.Arg384Lys Uncertain significance ★ ⚠ same type
FGR p.Arg465Trp 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/fgr-p-asp254 (accessed [today's date]).

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