Is FCGR3B p.Val104= (c.312C>A) pathogenic?

FCGR3B p.Val104= (c.312C>A) is classified Benign in FCGR3B (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-01). Low-frequency (popmax 1.09%, nfe).

How common is FCGR3B p.Val104= (c.312C>A) in the general population?

FCGR3B p.Val104= (c.312C>A) is low-frequency (popmax 1.09%, nfe) (gnomAD).

FCGR3B p.Val104=

c.312C>A · rs200303549 · VCV2639515

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.09%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.05	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -6.4	GERP 2.2
Overall
CADD	6.902	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.09% European (non-Finnish) · 11,918/1,090,298 alleles

Filtering AF 1.08% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.07%

Overall 1.03% 14,776/1,431,338 alleles · low-frequency exomes 13,944/1,354,350 · genomes 832/76,988 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	3.72%	27
Finnishnot grpmax-eligible	3.26%	31
European (non-Finnish)grpmax	1.09%	91
Remaining individualsnot grpmax-eligible	0.789%	127
Admixed American	0.464%	215
South Asian	0.437%	229
Middle Eastern	0.275%	363
African / African-American	0.205%	488
Ashkenazi Jewishnot grpmax-eligible	0.135%	738
East Asian	0.00328%	30,464

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val104=
Coding: c.312C>A
MANE Select: NM_001244753
dbSNP: rs200303549
Type: single nucleotide variant
Location: chr1:161629785 (GRCh38)
Gene constraint: LOEUF 1.466 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.04 · 6 PDB
Residue 104: 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-val104 (accessed [today's date]).

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