Is FGR p.Asn217Ser (c.650A>G) pathogenic?

FGR p.Asn217Ser (c.650A>G) is classified Likely benign in FGR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-23). AlphaMissense: likely benign (0.053); Ultra-rare (popmax 0.0527%, sas).

How common is FGR p.Asn217Ser (c.650A>G) in the general population?

FGR p.Asn217Ser (c.650A>G) is ultra-rare (popmax 0.0527%, sas) (gnomAD).

What do computational predictors say about FGR p.Asn217Ser (c.650A>G)?

AlphaMissense predicts likely benign (score 0.053) — an in-silico prediction, not a clinical call.

FGR p.Asn217Ser

c.650A>G · rs771875645 · VCV2550106

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.053 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0527%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.053	likely benign
REVEL	0.204	benign-leaning
SaProt	LLR -6.47	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -0.87, phastCons 0.008
Regional constraint	o/e 0.74	unconstrained · MANE · 11 kb · p 7.9e-12 · regional, not allelic
Overall
CADD	3.723	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 0.0527% South Asian · 48/91,088 alleles

Filtering AF 0.0408% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0366%

Overall 0.00297% 48/1,614,012 alleles · ultra-rare

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.Asn217Ser
Coding: c.650A>G
MANE Select: NM_005248
dbSNP: rs771875645
Type: single nucleotide variant
Location: chr1:27616889 (GRCh38)
Gene constraint: LOEUF 0.556 · pLI 0.50 (gnomAD)
Structure: AlphaFold pLDDT 83.00 · 7 PDB
Residue 217: the sh2 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-asn217ser (accessed [today's date]).

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