Is FPGS p.Arg5Trp (c.13C>T) pathogenic?

FPGS p.Arg5Trp (c.13C>T) is classified Uncertain significance in FPGS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-10). AlphaMissense: likely benign (0.1778); Ultra-rare (popmax 0.0257%, mid).

How common is FPGS p.Arg5Trp (c.13C>T) in the general population?

FPGS p.Arg5Trp (c.13C>T) is ultra-rare (popmax 0.0257%, mid) (gnomAD).

What do computational predictors say about FPGS p.Arg5Trp (c.13C>T)?

AlphaMissense predicts likely benign (score 0.1778) — an in-silico prediction, not a clinical call.

FPGS p.Arg5Trp

c.13C>T · rs1008651151 · VCV2466737

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1778 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0257%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1778	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -6.41	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 0.005	GERP -1.1
Regional constraint	o/e 1.16	unconstrained · MANE · 1,383 bp · p 0.11 · regional, not allelic
Overall
CADD	16.77	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0257% Middle Eastern · 1/3,890 alleles

Filtering AF 0.00531% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00488%

Overall 0.00574% 80/1,393,680 alleles · ultra-rare exomes 71/1,242,020 · genomes 9/151,660 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0257%	3,890
Ashkenazi Jewishnot grpmax-eligible	0.0133%	7,501
European (non-Finnish)	0.00657%	15,216
Remaining individualsnot grpmax-eligible	0.00376%	26,561
Admixed American	0.00343%	29,184
South Asian	0.00309%	32,380

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.Arg5Trp
Coding: c.13C>T
MANE Select: NM_004957
dbSNP: rs1008651151
Type: single nucleotide variant
Location: chr9:127802937 (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.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
FPGS p.Ala451Thr 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-arg5trp (accessed [today's date]).

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