Is FGR p.Arg118Trp (c.352C>T) pathogenic?

FGR p.Arg118Trp (c.352C>T) is classified Uncertain significance in FGR (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-11-04). AlphaMissense: likely benign (0.2468); Very rare (popmax 0.00878%, sas).

How common is FGR p.Arg118Trp (c.352C>T) in the general population?

FGR p.Arg118Trp (c.352C>T) is very rare (popmax 0.00878%, sas) (gnomAD).

What do computational predictors say about FGR p.Arg118Trp (c.352C>T)?

AlphaMissense predicts likely benign (score 0.2468) — an in-silico prediction, not a clinical call.

FGR p.Arg118Trp

c.352C>T · rs774209795 · VCV983543

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2468 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00878%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2468	likely benign
REVEL	0.408	indeterminate
SaProt	LLR -14.34	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP 2.4, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 11 kb · p 7.9e-12 · regional, not allelic
Overall
CADD	26.1	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 0.00878% South Asian · 8/91,068 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.00124% 20/1,613,732 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00878%	11,384
African / African-American	0.00134%	74,850
European (non-Finnish)	0.000932%	107,262

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.Arg118Trp
Coding: c.352C>T
MANE Select: NM_005248
dbSNP: rs774209795
Type: single nucleotide variant
Location: chr1:27621635 (GRCh38)
Gene constraint: LOEUF 0.556 · pLI 0.50 (gnomAD)
Structure: AlphaFold pLDDT 83.00 · 7 PDB
Residue 118: the sh3 domain; a β-strand

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.Asp254= 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

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-arg118trp (accessed [today's date]).

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