Is FASN p.Ser2236Phe (c.6707C>T) pathogenic?

FASN p.Ser2236Phe (c.6707C>T) is classified Benign in FASN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-21). AlphaMissense: likely benign (0.1549); Low-frequency (popmax 1.28%, sas); Associated with Epileptic encephalopathy.

What condition is associated with FASN p.Ser2236Phe (c.6707C>T)?

FASN p.Ser2236Phe (c.6707C>T) is associated with Epileptic encephalopathy (ClinVar).

How common is FASN p.Ser2236Phe (c.6707C>T) in the general population?

FASN p.Ser2236Phe (c.6707C>T) is low-frequency (popmax 1.28%, sas) (gnomAD).

What do computational predictors say about FASN p.Ser2236Phe (c.6707C>T)?

AlphaMissense predicts likely benign (score 0.1549) — an in-silico prediction, not a clinical call.

FASN p.Ser2236Phe

c.6707C>T · rs201913904 · VCV767251

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1549 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.28%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Epileptic encephalopathy

Computational evidence

Protein change
AlphaMissense	0.1549	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -10.55	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -3.5, phastCons 0.099
Regional constraint	o/e 0.85	unconstrained · MANE · 5,668 bp · p 2e-08 · regional, not allelic
Overall
CADD	13.71	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 1.28% South Asian · 1,158/90,282 alleles

Filtering AF 1.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.2%

Overall 0.0795% 1,280/1,609,130 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.28%	78
Middle Eastern	0.188%	531
Remaining individualsnot grpmax-eligible	0.0562%	1,780
Admixed American	0.0185%	5,398
European (non-Finnish)	0.00526%	19,012
African / African-American	0.004%	25,012

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.Ser2236Phe
Coding: c.6707C>T
MANE Select: NM_004104
dbSNP: rs201913904
Type: single nucleotide variant
Location: chr17:82080811 (GRCh38)
Gene constraint: LOEUF 0.284 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.65 · 34 PDB
Residue 2236: a modified residue (phosphoserine); the 'thioesterase' 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.Ser2236= Likely benign ★ 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-ser2236phe (accessed [today's date]).

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