Is FPGS p.Arg30Trp (c.88C>T) pathogenic?

FPGS p.Arg30Trp (c.88C>T) is classified Uncertain significance in FPGS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-27). AlphaMissense: likely benign (0.1343); Ultra-rare (popmax 0.0964%, afr).

How common is FPGS p.Arg30Trp (c.88C>T) in the general population?

FPGS p.Arg30Trp (c.88C>T) is ultra-rare (popmax 0.0964%, afr) (gnomAD).

What do computational predictors say about FPGS p.Arg30Trp (c.88C>T)?

AlphaMissense predicts likely benign (score 0.1343) — an in-silico prediction, not a clinical call.

FPGS p.Arg30Trp

c.88C>T · rs757514010 · VCV2387790

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1343 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0964%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1343	likely benign
REVEL	0.164	moderately benign-leaning
SaProt	LLR -10.66	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP 1.7, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 1,383 bp · p 0.11 · regional, not allelic
Overall
CADD	22.5	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 0.0964% African / African-American · 65/67,442 alleles

Filtering AF 0.0775% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0707%

Overall 0.00471% 69/1,465,212 alleles · ultra-rare exomes 29/1,313,156 · genomes 40/152,056 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0964%	1,038
Remaining individualsnot grpmax-eligible	0.00531%	18,821
European (non-Finnish)	8.95e-05%	1,116,852

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: FPGS
Protein: p.Arg30Trp
Coding: c.88C>T
MANE Select: NM_004957
dbSNP: rs757514010
Type: single nucleotide variant
Location: chr9:127803012 (GRCh38)
Gene constraint: LOEUF 1.174 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.05

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

Similar variants

FPGS p.Arg30Gln Uncertain significance ★ ⚠ same residue
FPGS p.Ile22Val Benign ★★ same type
FPGS p.Ala10Ser Uncertain significance ★ ⚠ same type
FPGS p.Ala15Gly Uncertain significance ★ ⚠ same type
FPGS p.Ala19Gly Uncertain significance ★ ⚠ same type
FPGS p.Ala307Ser Uncertain significance ★ ⚠ same type
FPGS p.Ala395Thr Uncertain significance ★ ⚠ same type
FPGS p.Ala423Gly 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/fpgs-p-arg30trp (accessed [today's date]).

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