Is FASN p.Ser1237Asn (c.3710G>A) pathogenic?

FASN p.Ser1237Asn (c.3710G>A) is classified Uncertain significance in FASN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-14). AlphaMissense: likely benign (0.111); Ultra-rare (popmax 0.0478%, sas); Associated with Epileptic encephalopathy.

What condition is associated with FASN p.Ser1237Asn (c.3710G>A)?

FASN p.Ser1237Asn (c.3710G>A) is associated with Epileptic encephalopathy (ClinVar).

How common is FASN p.Ser1237Asn (c.3710G>A) in the general population?

FASN p.Ser1237Asn (c.3710G>A) is ultra-rare (popmax 0.0478%, sas) (gnomAD).

What do computational predictors say about FASN p.Ser1237Asn (c.3710G>A)?

AlphaMissense predicts likely benign (score 0.111) — an in-silico prediction, not a clinical call.

FASN p.Ser1237Asn

c.3710G>A · rs548731852 · VCV1381012

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.111 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0478%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Epileptic encephalopathy

Computational evidence

Protein change
AlphaMissense	0.111	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -6.92	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 0.61	GERP -2.3
Regional constraint	o/e 0.96	unconstrained · MANE · 5,620 bp · p 0.14 · regional, not allelic
Overall
CADD	6.216	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 0.0478% South Asian · 42/87,858 alleles

Filtering AF 0.0363% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0323%

Overall 0.00329% 52/1,580,014 alleles · ultra-rare exomes 48/1,427,670 · genomes 4/152,344 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0478%	2,092
African / African-American	0.00802%	12,465
Remaining individualsnot grpmax-eligible	0.00487%	20,525
European (non-Finnish)	8.55e-05%	1,169,364

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.Ser1237Asn
Coding: c.3710G>A
MANE Select: NM_004104
dbSNP: rs548731852
Type: single nucleotide variant
Location: chr17:82086276 (GRCh38)
Gene constraint: LOEUF 0.284 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.65 · 34 PDB
Residue 1237: a β-strand

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 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
FASN p.Ala1686Thr 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-ser1237asn (accessed [today's date]).

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