Is FDPS p.Ser63= (c.189C>T) pathogenic?

FDPS p.Ser63= (c.189C>T) is classified Benign in FDPS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-03-23). Rare (popmax 0.141%, nfe); Associated with FDPS-related disorder.

What condition is associated with FDPS p.Ser63= (c.189C>T)?

FDPS p.Ser63= (c.189C>T) is associated with FDPS-related disorder (ClinVar).

How common is FDPS p.Ser63= (c.189C>T) in the general population?

FDPS p.Ser63= (c.189C>T) is rare (popmax 0.141%, nfe) (gnomAD).

FDPS p.Ser63=

c.189C>T · rs143038155 · VCV3041400

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.141%, nfe)

Conditions

FDPS-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.30 · evaluated, not missing
Pangolin	Δ0.31	gain · loss 0.16 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 0.55	GERP 2, phastCons 0.97
Overall
CADD	16.61	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.141% European (non-Finnish) · 1,664/1,180,020 alleles

Filtering AF 0.135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.133%

Overall 0.185% 2,989/1,613,606 alleles · rare exomes 2,610/1,461,302 · genomes 379/152,304 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	4.61%	22
Finnishnot grpmax-eligible	1.79%	56
Remaining individualsnot grpmax-eligible	0.186%	538
European (non-Finnish)grpmax	0.141%	709
African / African-American	0.02%	5,001
Middle Eastern	0.0178%	5,604
Admixed American	0.00666%	15,006
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser63=
Coding: c.189C>T
MANE Select: NM_002004
dbSNP: rs143038155
Type: single nucleotide variant
Location: chr1:155310055 (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.Arg48Cys Benign same condition
FDPS p.Ile120Thr 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-ser63 (accessed [today's date]).

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