Is FCGR2A p.His167Arg (c.500A>G) pathogenic?

FCGR2A p.His167Arg (c.500A>G) is classified Benign in FCGR2A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2016-03-28). AlphaMissense: likely benign (0.1036); Common (popmax 54.6%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about FCGR2A p.His167Arg (c.500A>G)?

AlphaMissense predicts likely benign (score 0.1036) — an in-silico prediction, not a clinical call.

FCGR2A p.His167Arg

Q: How common is FCGR2A p.His167Arg (c.500A>G) in the general population?

FCGR2A p.His167Arg (c.500A>G) is common (popmax 54.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.500A>G · rs1801274 · VCV14823

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1036 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 54.6%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1036	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -7.09	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 -10	GERP -3.7
Regional constraint	o/e 0.72	unconstrained · MANE · 5,367 bp · p 1e-05 · regional, not allelic
Overall
CADD	0.002	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 54.6% African / African-American · 40,874/74,924 alleles

Filtering AF 54.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 53.9%

Overall 50.3% 811,016/1,613,712 alleles · common exomes 734,636/1,461,666 · genomes 76,380/152,046 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	54.6%	2
European (non-Finnish)	51.9%	2
Admixed American	50.7%	2
Remaining individualsnot grpmax-eligible	50.2%	2
Finnishnot grpmax-eligible	50.1%	2
Middle Eastern	44.2%	2
South Asian	41.5%	2
Ashkenazi Jewishnot grpmax-eligible	40.5%	2
Amishnot grpmax-eligible	36.8%	3
East Asian	26%	4

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.

Cancer therapy — CIViC

Disease	Therapies	Level	Significance
Breast Cancer		B
HER2 Positive Breast Cancer	Trastuzumab	B	Sensitivity/Response

Variant & gene context

Gene: FCGR2A
Protein: p.His167Arg
Coding: c.500A>G
MANE Select: NM_001136219
dbSNP: rs1801274
Type: single nucleotide variant
Location: chr1:161509955 (GRCh38)
Gene constraint: LOEUF 0.922 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.04 · 10 PDB
Residue 167: a UniProt-annotated variant site (probable risk factor for lupus nephritis; does not efficiently recognize igg2); 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.Pro215= Benign ★★ same type
FCGR2A p.Pro293= Benign ★★ same type
FCGR2A p.Ser70= Benign/Likely 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-his167arg (accessed [today's date]).

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