Is FASN p.Asp2469= (c.7407C>T) pathogenic?

FASN p.Asp2469= (c.7407C>T) is classified Likely benign in FASN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-19). Rare (popmax 0.102%, amr); Associated with Epileptic encephalopathy.

What condition is associated with FASN p.Asp2469= (c.7407C>T)?

FASN p.Asp2469= (c.7407C>T) is associated with Epileptic encephalopathy (ClinVar).

How common is FASN p.Asp2469= (c.7407C>T) in the general population?

FASN p.Asp2469= (c.7407C>T) is rare (popmax 0.102%, amr) (gnomAD).

FASN p.Asp2469=

c.7407C>T · rs144413151 · VCV531150

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.102%, amr)

Conditions

Epileptic encephalopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP -3.6
Overall
CADD	4.722	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.102% Admixed American · 61/60,032 alleles

Filtering AF 0.0811% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0738%

Overall 0.0214% 345/1,613,056 alleles · rare exomes 272/1,460,712 · genomes 73/152,344 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.102%	984
Middle Eastern	0.0825%	1,212
Remaining individualsnot grpmax-eligible	0.056%	1,786
East Asian	0.0401%	2,493
African / African-American	0.04%	2,502
Ashkenazi Jewishnot grpmax-eligible	0.0372%	2,691
European (non-Finnish)	0.0157%	6,378

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.Asp2469=
Coding: c.7407C>T
MANE Select: NM_004104
dbSNP: rs144413151
Type: single nucleotide variant
Location: chr17:82079272 (GRCh38)
Gene constraint: LOEUF 0.284 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.65 · 34 PDB
Residue 2469: a β-strand; 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 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-asp2469 (accessed [today's date]).

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