Is FCGRT p.Pro183Ser (c.547C>T) pathogenic?

FCGRT p.Pro183Ser (c.547C>T) is classified Uncertain significance in FCGRT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-07). AlphaMissense: likely pathogenic (0.7005); Ultra-rare (popmax 0.0416%, afr).

How common is FCGRT p.Pro183Ser (c.547C>T) in the general population?

FCGRT p.Pro183Ser (c.547C>T) is ultra-rare (popmax 0.0416%, afr) (gnomAD).

What do computational predictors say about FCGRT p.Pro183Ser (c.547C>T)?

AlphaMissense predicts likely pathogenic (score 0.7005) — an in-silico prediction, not a clinical call.

FCGRT p.Pro183Ser

c.547C>T · VCV4024160

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7005 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0416%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7005	likely pathogenic
REVEL	0.118	moderately benign-leaning
SaProt	LLR -9.70	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 1.3, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 12 kb · p 0.36 · regional, not allelic
Overall
CADD	23.4	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 0.0416% African / African-American · 31/74,594 alleles

Filtering AF 0.0301% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0261%

Overall 0.00214% 34/1,587,420 alleles · ultra-rare exomes 15/1,435,122 · genomes 19/152,298 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0416%	2,406
East Asian	0.00225%	44,458
Admixed American	0.00172%	58,054
Remaining individualsnot grpmax-eligible	0.00163%	61,188

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.Pro183Ser
Coding: c.547C>T
MANE Select: NM_001136019
Type: single nucleotide variant
Location: chr19:49514432 (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.Pro183Arg 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-pro183ser (accessed [today's date]).

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