Is FASN p.Ala656= (c.1968C>T) pathogenic?

FASN p.Ala656= (c.1968C>T) is classified Benign in FASN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-28). Common (popmax 5.73%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Epileptic encephalopathy.

What condition is associated with FASN p.Ala656= (c.1968C>T)?

FASN p.Ala656= (c.1968C>T) is associated with Epileptic encephalopathy (ClinVar).

FASN p.Ala656=

Q: How common is FASN p.Ala656= (c.1968C>T) in the general population?

FASN p.Ala656= (c.1968C>T) is common (popmax 5.73%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1968C>T · rs45540245 · VCV462013

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 5.73%, afr) — too common for a highly-penetrant pathogenic allele

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 -2.8	GERP -2.8
Overall
CADD	0.053	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.73% African / African-American · 4,300/75,016 alleles

Filtering AF 5.59% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.53%

Overall 0.299% 4,821/1,612,736 alleles · common exomes 2,301/1,460,488 · genomes 2,520/152,248 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.73%	17
Admixed American	0.427%	234
Remaining individualsnot grpmax-eligible	0.354%	283
Middle Eastern	0.115%	866
South Asian	0.00878%	11,385
European (non-Finnish)	0.00246%	40,689

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.Ala656=
Coding: c.1968C>T
MANE Select: NM_004104
dbSNP: rs45540245
Type: single nucleotide variant
Location: chr17:82089382 (GRCh38)
Gene constraint: LOEUF 0.284 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.65 · 34 PDB
Residue 656: an α-helix; 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 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-ala656 (accessed [today's date]).

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