Is FDPS p.Pro401Thr (c.1201C>A) pathogenic?

FDPS p.Pro401Thr (c.1201C>A) is classified Uncertain significance in FDPS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-10). AlphaMissense: likely benign (0.1014); Absent from gnomAD v4.1.

How common is FDPS p.Pro401Thr (c.1201C>A) in the general population?

FDPS p.Pro401Thr (c.1201C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FDPS p.Pro401Thr (c.1201C>A)?

AlphaMissense predicts likely benign (score 0.1014) — an in-silico prediction, not a clinical call.

FDPS p.Pro401Thr

c.1201C>A · VCV3514563

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1014 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1014	likely benign
REVEL	0.112	moderately benign-leaning
SaProt	LLR -11.62	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 2.7	GERP 2.1, phastCons 0.99
Regional constraint	o/e 0.79	unconstrained · MANE · 11 kb · p 1.1e-06 · regional, not allelic
Overall
CADD	15.4	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

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: FDPS
Protein: p.Pro401Thr
Coding: c.1201C>A
MANE Select: NM_002004
Type: single nucleotide variant
Location: chr1:155320550 (GRCh38)
Gene constraint: LOEUF 0.744 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.27 · 92 PDB

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

Similar variants

FDPS c.684+2T>G Likely pathogenic ★ same type
FDPS p.Ala119Val Uncertain significance ★ ⚠ same type
FDPS p.Arg110Gly Uncertain significance ★ ⚠ same type
FDPS p.Arg110Trp Uncertain significance ★ ⚠ same type
FDPS p.Arg214Gln Uncertain significance ★ ⚠ same type
FDPS p.Arg23Gln Uncertain significance ★ ⚠ same type
FDPS p.Arg23Trp Uncertain significance ★ ⚠ same type
FDPS p.Arg25Lys 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/fdps-p-pro401thr (accessed [today's date]).

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