Is FCGRT p.Pro183Arg (c.548C>G) pathogenic?

FCGRT p.Pro183Arg (c.548C>G) is classified Uncertain significance in FCGRT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-09). AlphaMissense: likely pathogenic (0.6973); Very rare (popmax 0.00134%, afr).

How common is FCGRT p.Pro183Arg (c.548C>G) in the general population?

FCGRT p.Pro183Arg (c.548C>G) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about FCGRT p.Pro183Arg (c.548C>G)?

AlphaMissense predicts likely pathogenic (score 0.6973) — an in-silico prediction, not a clinical call.

FCGRT p.Pro183Arg

c.548C>G · rs554770888 · VCV2546032

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6973 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6973	likely pathogenic
REVEL	0.129	moderately benign-leaning
SaProt	LLR -11.61	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.5	GERP 0.062, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 12 kb · p 0.36 · regional, not allelic
Overall
CADD	21.9	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 0.00134% African / African-American · 1/74,540 alleles

Overall 6.31e-05% 1/1,585,838 alleles · very rare exomes 1/1,433,582 · genomes 0/152,256 · 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: FCGRT
Protein: p.Pro183Arg
Coding: c.548C>G
MANE Select: NM_001136019
dbSNP: rs554770888
Type: single nucleotide variant
Location: chr19:49514433 (GRCh38)
Gene constraint: LOEUF 0.706 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 85.73 · 31 PDB
Residue 183: an α-helix; the 'alpha-2' region

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

Similar variants

FCGRT p.Pro183Ser Uncertain significance ★ ⚠ same residue
FCGRT p.Lys132Asn Benign ★★ same type
FCGRT p.Pro42= Benign ★★ same type
FCGRT p.Thr340= Benign ★★ same type
FCGRT p.Ala280Thr Uncertain significance ★ ⚠ same type
FCGRT p.Ala280Val Uncertain significance ★ ⚠ same type
FCGRT p.Ala283Thr Uncertain significance ★ ⚠ same type
FCGRT p.Ala283Val 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/fcgrt-p-pro183arg (accessed [today's date]).

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