Is FGR p.Pro161Leu (c.482C>T) pathogenic?

FGR p.Pro161Leu (c.482C>T) is classified Uncertain significance in FGR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-13). AlphaMissense: likely benign (0.0696); Ultra-rare (popmax 0.016%, afr).

How common is FGR p.Pro161Leu (c.482C>T) in the general population?

FGR p.Pro161Leu (c.482C>T) is ultra-rare (popmax 0.016%, afr) (gnomAD).

What do computational predictors say about FGR p.Pro161Leu (c.482C>T)?

AlphaMissense predicts likely benign (score 0.0696) — an in-silico prediction, not a clinical call.

FGR p.Pro161Leu

c.482C>T · rs535305096 · VCV2532545

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0696 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0696	likely benign
REVEL	0.288	benign-leaning
SaProt	LLR -10.34	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.9	GERP -0.076
Regional constraint	o/e 0.74	unconstrained · MANE · 11 kb · p 7.9e-12 · regional, not allelic
Overall
CADD	14.66	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 0.016% African / African-American · 12/75,060 alleles

Filtering AF 0.0092% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0072%

Overall 0.000805% 13/1,614,190 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,255
Admixed American	0.00167%	60,032

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.Pro161Leu
Coding: c.482C>T
MANE Select: NM_005248
dbSNP: rs535305096
Type: single nucleotide variant
Location: chr1:27617243 (GRCh38)
Gene constraint: LOEUF 0.556 · pLI 0.50 (gnomAD)
Structure: AlphaFold pLDDT 83.00 · 7 PDB
Residue 161: the sh2 domain

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-pro161leu (accessed [today's date]).

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