Is FCGR2A p.Arg142Lys (c.425G>A) pathogenic?

FCGR2A p.Arg142Lys (c.425G>A) is classified Uncertain significance in FCGR2A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely benign (0.1602); Very rare (popmax 0.000763%, nfe).

How common is FCGR2A p.Arg142Lys (c.425G>A) in the general population?

FCGR2A p.Arg142Lys (c.425G>A) is very rare (popmax 0.000763%, nfe) (gnomAD).

What do computational predictors say about FCGR2A p.Arg142Lys (c.425G>A)?

AlphaMissense predicts likely benign (score 0.1602) — an in-silico prediction, not a clinical call.

FCGR2A p.Arg142Lys

c.425G>A · VCV4256432

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1602 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1602	likely benign
REVEL	0.203	benign-leaning
SaProt	LLR -10.29	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 1.8	GERP 0.67, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 5,367 bp · p 1e-05 · regional, not allelic
Overall
CADD	22.5	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 0.000763% European (non-Finnish) · 9/1,180,032 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000558% 9/1,614,200 alleles · very rare exomes 9/1,461,892 · genomes 0/152,308 · joint denominator

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.Arg142Lys
Coding: c.425G>A
MANE Select: NM_001136219
Type: single nucleotide variant
Location: chr1:161509880 (GRCh38)
Gene constraint: LOEUF 0.922 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.04 · 10 PDB
Residue 142: a β-strand; the ig-like c2-type 2 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-arg142lys (accessed [today's date]).

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