Is FASN p.Ala487Ser (c.1459G>T) pathogenic?

FASN p.Ala487Ser (c.1459G>T) is classified Uncertain significance in FASN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-10). AlphaMissense: likely benign (0.0773); Very rare (popmax 0.00134%, afr); Associated with Epileptic encephalopathy.

What condition is associated with FASN p.Ala487Ser (c.1459G>T)?

FASN p.Ala487Ser (c.1459G>T) is associated with Epileptic encephalopathy (ClinVar).

How common is FASN p.Ala487Ser (c.1459G>T) in the general population?

FASN p.Ala487Ser (c.1459G>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about FASN p.Ala487Ser (c.1459G>T)?

AlphaMissense predicts likely benign (score 0.0773) — an in-silico prediction, not a clinical call.

FASN p.Ala487Ser

c.1459G>T · rs372434423 · VCV1949584

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0773 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Epileptic encephalopathy

Computational evidence

Protein change
AlphaMissense	0.0773	likely benign
REVEL	0.009	strongly benign-leaning
SaProt	LLR -5.78	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 -11	GERP -3.3
Regional constraint	o/e 0.98	unconstrained · MANE · 973 bp · p 0.76 · regional, not allelic
Overall
CADD	0.003	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 0.00134% African / African-American · 1/74,774 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000312% 5/1,601,170 alleles · very rare exomes 3/1,448,924 · genomes 2/152,246 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,774
European (non-Finnish)	0.000341%	293,555

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: FASN
Protein: p.Ala487Ser
Coding: c.1459G>T
MANE Select: NM_004104
dbSNP: rs372434423
Type: single nucleotide variant
Location: chr17:82091255 (GRCh38)
Gene constraint: LOEUF 0.284 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.65 · 34 PDB
Residue 487: the 'acyl and malonyl transferases' region

Full FASN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Epileptic encephalopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FASN p.Ala487Thr Uncertain significance ★★ ⚠ same residue
FASN c.3733-3C>T Uncertain significance ★★ same condition
FASN c.655+3G>T Uncertain significance ★★ same condition
FASN p.Ala1073Ser Uncertain significance ★★ ⚠ same condition
FASN p.Ala1272Val Uncertain significance ★★ ⚠ same condition
FASN p.Ala1285Val Uncertain significance ★★ ⚠ same condition
FASN p.Ala1569Ser Uncertain significance ★★ ⚠ same condition
FASN p.Ala1684Thr Uncertain significance ★★ same condition

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/fasn-p-ala487ser (accessed [today's date]).

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