Is FCGR3B p.Val176Phe (c.526G>T) pathogenic?

FCGR3B p.Val176Phe (c.526G>T) is classified Likely benign in FCGR3B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-01). AlphaMissense: likely benign (0.2065); Rare (popmax 0.487%, sas).

How common is FCGR3B p.Val176Phe (c.526G>T) in the general population?

FCGR3B p.Val176Phe (c.526G>T) is rare (popmax 0.487%, sas) (gnomAD).

What do computational predictors say about FCGR3B p.Val176Phe (c.526G>T)?

AlphaMissense predicts likely benign (score 0.2065) — an in-silico prediction, not a clinical call.

FCGR3B p.Val176Phe

c.526G>T · rs200215055 · VCV3250532

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2065 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.487%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2065	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	LLR -7.38	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 -2.8	GERP -9.4
Regional constraint	o/e 0.90	unconstrained · MANE · 1,801 bp · p 0.28 · regional, not allelic
Overall
CADD	1.355	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 0.487% South Asian · 441/90,578 alleles

Filtering AF 0.449% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.435%

Overall 0.156% 2,507/1,608,958 alleles · rare exomes 2,273/1,458,570 · genomes 234/150,388 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.487%	205
Admixed American	0.206%	485
Remaining individualsnot grpmax-eligible	0.181%	551
Ashkenazi Jewishnot grpmax-eligible	0.162%	616
European (non-Finnish)	0.144%	696
African / African-American	0.0937%	1,068
Middle Eastern	0.0497%	2,012
East Asian	0.0201%	4,974
Finnishnot grpmax-eligible	0.0141%	7,086

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: FCGR3B
Protein: p.Val176Phe
Coding: c.526G>T
MANE Select: NM_001244753
dbSNP: rs200215055
Type: single nucleotide variant
Location: chr1:161626196 (GRCh38)
Gene constraint: LOEUF 1.466 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.04 · 6 PDB
Residue 176: the ig-like c2-type 2 domain; a β-strand

Full FCGR3B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FCGR3B p.Asn65Ser Benign ★★ same type
FCGR3B p.Ile106Val Benign ★★ same type
FCGR3B p.Ala162Thr Uncertain significance ★ ⚠ same type
FCGR3B p.Ala195Thr Uncertain significance ★ ⚠ same type
FCGR3B p.Ala220Glu Uncertain significance ★ ⚠ same type
FCGR3B p.Ala79Thr Uncertain significance ★ ⚠ same type
FCGR3B p.Arg173Lys Uncertain significance ★ ⚠ same type
FCGR3B p.Arg88Thr 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/fcgr3b-p-val176phe (accessed [today's date]).

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