Is FDPS p.Val364Ala (c.1091T>C) pathogenic?

FDPS p.Val364Ala (c.1091T>C) is classified Benign in FDPS (ClinVar, No assertion criteria, 2 submitters; last evaluated 2019-04-26). AlphaMissense: likely benign (0.2918); Low-frequency (popmax 2.77%, nfe); Associated with FDPS-related disorder.

What condition is associated with FDPS p.Val364Ala (c.1091T>C)?

FDPS p.Val364Ala (c.1091T>C) is associated with FDPS-related disorder (ClinVar).

How common is FDPS p.Val364Ala (c.1091T>C) in the general population?

FDPS p.Val364Ala (c.1091T>C) is low-frequency (popmax 2.77%, nfe) (gnomAD).

What do computational predictors say about FDPS p.Val364Ala (c.1091T>C)?

AlphaMissense predicts likely benign (score 0.2918) — an in-silico prediction, not a clinical call.

FDPS p.Val364Ala

c.1091T>C · rs41314549 · VCV684523

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2918 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.77%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

FDPS-related disorder

Computational evidence

Protein change
AlphaMissense	0.2918	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -5.76	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 7.8	GERP 2.1, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 11 kb · p 1.1e-06 · regional, not allelic
Overall
CADD	25.9	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 2.77% European (non-Finnish) · 32,668/1,179,926 alleles

Filtering AF 2.74% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.73%

Overall 2.33% 37,621/1,613,526 alleles · low-frequency

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	2.77%	36
Ashkenazi Jewishnot grpmax-eligible	2.71%	37
Remaining individualsnot grpmax-eligible	2.28%	44
South Asian	1.38%	72
Admixed American	1.3%	77
Middle Eastern	1.26%	79
Finnishnot grpmax-eligible	0.442%	226
Amishnot grpmax-eligible	0.439%	228
African / African-American	0.436%	229
East Asian	0.00446%	22,434

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.Val364Ala
Coding: c.1091T>C
MANE Select: NM_002004
dbSNP: rs41314549
Type: single nucleotide variant
Location: chr1:155320440 (GRCh38)
Gene constraint: LOEUF 0.744 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.27 · 92 PDB
Residue 364: a UniProt-annotated variant site (in); an α-helix

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.Ser63= Benign same condition
FDPS p.Tyr219= Likely 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-val364ala (accessed [today's date]).

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