Is FCGR2A p.Pro39Gln (c.116C>A) pathogenic?

FCGR2A p.Pro39Gln (c.116C>A) is classified Uncertain significance in FCGR2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-17). AlphaMissense: likely benign (0.0816); Very rare (popmax 0.005%, amr).

How common is FCGR2A p.Pro39Gln (c.116C>A) in the general population?

FCGR2A p.Pro39Gln (c.116C>A) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about FCGR2A p.Pro39Gln (c.116C>A)?

AlphaMissense predicts likely benign (score 0.0816) — an in-silico prediction, not a clinical call.

FCGR2A p.Pro39Gln

c.116C>A · VCV4525811

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0816 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0816	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -9.37	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.045	GERP -1.2
Regional constraint	o/e 0.72	unconstrained · MANE · 5,367 bp · p 1e-05 · regional, not allelic
Overall
CADD	18.11	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,008 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.00031% 5/1,614,104 alleles · very rare exomes 4/1,461,892 · genomes 1/152,212 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,003
African / African-American	0.00133%	74,936
European (non-Finnish)	8.47e-05%	1,180,048

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: FCGR2A
Protein: p.Pro39Gln
Coding: c.116C>A
MANE Select: NM_001136219
Type: single nucleotide variant
Location: chr1:161506343 (GRCh38)
Gene constraint: LOEUF 0.922 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.04 · 10 PDB
Residue 39: the ig-like c2-type 1 domain

Full FCGR2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FCGR2A c.780+1G>A Uncertain significance ★★ same type
FCGR2A p.Ser315Gly Uncertain significance ★★ ⚠ same type
FCGR2A c.365-11G>A Benign ★★ same type
FCGR2A p.Gln63Arg Benign ★★ same type
FCGR2A p.Gln63Ter Benign ★★ same type
FCGR2A p.His167Arg Benign ★★ same type
FCGR2A p.Pro215= Benign ★★ same type
FCGR2A p.Pro293= Benign ★★ 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/fcgr2a-p-pro39gln (accessed [today's date]).

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