Is FDPS p.Ile307Val (c.919A>G) pathogenic?

FDPS p.Ile307Val (c.919A>G) is classified Uncertain significance in FDPS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). AlphaMissense: likely benign (0.1405); Very rare (popmax 0.00891%, eas).

How common is FDPS p.Ile307Val (c.919A>G) in the general population?

FDPS p.Ile307Val (c.919A>G) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about FDPS p.Ile307Val (c.919A>G)?

AlphaMissense predicts likely benign (score 0.1405) — an in-silico prediction, not a clinical call.

FDPS p.Ile307Val

c.919A>G · rs754756693 · VCV3094325

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1405 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1405	likely benign
REVEL	0.136	moderately benign-leaning
SaProt	LLR -7.03	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 1.4	GERP -1.1, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 11 kb · p 1.1e-06 · regional, not allelic
Overall
CADD	15.9	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 0.00891% East Asian · 4/44,880 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000248% 4/1,614,188 alleles · very rare exomes 4/1,461,888 · genomes 0/152,300 · joint denominator

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.Ile307Val
Coding: c.919A>G
MANE Select: NM_002004
dbSNP: rs754756693
Type: single nucleotide variant
Location: chr1:155319683 (GRCh38)
Gene constraint: LOEUF 0.744 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.27 · 92 PDB
Residue 307: an α-helix

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-ile307val (accessed [today's date]).

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