Is FPGS p.Ala554Pro (c.1660G>C) pathogenic?

FPGS p.Ala554Pro (c.1660G>C) is classified Uncertain significance in FPGS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-12). AlphaMissense: likely benign (0.1638); Absent from gnomAD v4.1.

How common is FPGS p.Ala554Pro (c.1660G>C) in the general population?

FPGS p.Ala554Pro (c.1660G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FPGS p.Ala554Pro (c.1660G>C)?

AlphaMissense predicts likely benign (score 0.1638) — an in-silico prediction, not a clinical call.

FPGS p.Ala554Pro

c.1660G>C · rs2539045620 · VCV2318104

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1638 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1638	likely benign
REVEL	0.154	moderately benign-leaning
SaProt	LLR -4.97	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 7.5	GERP 0.51, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 4,907 bp · p 0.5 · regional, not allelic
Overall
CADD	17.12	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FPGS
Protein: p.Ala554Pro
Coding: c.1660G>C
MANE Select: NM_004957
dbSNP: rs2539045620
Type: single nucleotide variant
Location: chr9:127813500 (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-ala554pro (accessed [today's date]).

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