Is FDPS p.Arg48Cys (c.142C>T) pathogenic?

FDPS p.Arg48Cys (c.142C>T) is classified Benign in FDPS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-24). AlphaMissense: likely benign (0.1911); Low-frequency (popmax 1.91%, afr); Associated with FDPS-related disorder.

What condition is associated with FDPS p.Arg48Cys (c.142C>T)?

FDPS p.Arg48Cys (c.142C>T) is associated with FDPS-related disorder (ClinVar).

How common is FDPS p.Arg48Cys (c.142C>T) in the general population?

FDPS p.Arg48Cys (c.142C>T) is low-frequency (popmax 1.91%, afr) (gnomAD).

What do computational predictors say about FDPS p.Arg48Cys (c.142C>T)?

AlphaMissense predicts likely benign (score 0.1911) — an in-silico prediction, not a clinical call.

FDPS p.Arg48Cys

c.142C>T · rs35362111 · VCV3042548

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1911 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.91%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

FDPS-related disorder

Computational evidence

Protein change
AlphaMissense	0.1911	likely benign
REVEL	0.193	benign-leaning
SaProt	LLR -8.60	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 4.4	GERP 0.43, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 11 kb · p 1.1e-06 · regional, not allelic
Overall
CADD	26.8	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 1.91% African / African-American · 1,431/74,846 alleles

Filtering AF 1.83% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.8%

Overall 0.267% 4,291/1,604,308 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.91%	52
Remaining individualsnot grpmax-eligible	0.315%	318
Admixed American	0.302%	332
Middle Eastern	0.287%	348
European (non-Finnish)	0.201%	497
Finnishnot grpmax-eligible	0.108%	923
Ashkenazi Jewishnot grpmax-eligible	0.0782%	1,278
South Asian	0.0199%	5,031

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.Arg48Cys
Coding: c.142C>T
MANE Select: NM_002004
dbSNP: rs35362111
Type: single nucleotide variant
Location: chr1:155309931 (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

Disease context

FDPS-related disorder

Similar variants

FDPS p.Trp26Ter Uncertain significance ★ same condition
FDPS p.Ile120Thr Benign same condition
FDPS p.Ser63= Benign same condition
FDPS p.Tyr219= Likely benign same condition
FDPS p.Val364Ala Benign same condition
FDPS c.684+2T>G Likely pathogenic ★ same type
FDPS p.Ala119Val Uncertain significance ★ ⚠ same type
FDPS p.Arg110Gly 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-arg48cys (accessed [today's date]).

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