Is FDPS p.Arg5Cys (c.13C>T) pathogenic?

FDPS p.Arg5Cys (c.13C>T) is classified Uncertain significance in FDPS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-14). AlphaMissense: likely benign (0.2494); Very rare (popmax 0.00183%, nfe).

How common is FDPS p.Arg5Cys (c.13C>T) in the general population?

FDPS p.Arg5Cys (c.13C>T) is very rare (popmax 0.00183%, nfe) (gnomAD).

What do computational predictors say about FDPS p.Arg5Cys (c.13C>T)?

AlphaMissense predicts likely benign (score 0.2494) — an in-silico prediction, not a clinical call.

FDPS p.Arg5Cys

c.13C>T · VCV4024333

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2494 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00183%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2494	likely benign
REVEL	0.136	moderately benign-leaning
SaProt	LLR -7.94	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3	GERP 0.47, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 11 kb · p 1.1e-06 · regional, not allelic
Overall
CADD	23.4	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 0.00183% European (non-Finnish) · 21/1,144,594 alleles

Filtering AF 0.00118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.001%

Overall 0.00141% 22/1,556,676 alleles · very rare exomes 21/1,404,538 · genomes 1/152,138 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00183%	54,505
Remaining individualsnot grpmax-eligible	0.00167%	60,052

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: FDPS
Protein: p.Arg5Cys
Coding: c.13C>T
MANE Select: NM_002004
Type: single nucleotide variant
Location: chr1:155309802 (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-arg5cys (accessed [today's date]).

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