Is FASN p.Pro208= (c.624C>T) pathogenic?

FASN p.Pro208= (c.624C>T) is classified Benign in FASN (ClinVar, Single submitter, 2 submitters; last evaluated 2026-01-28). Low-frequency (popmax 2.1%, afr); Associated with Epileptic encephalopathy.

What condition is associated with FASN p.Pro208= (c.624C>T)?

FASN p.Pro208= (c.624C>T) is associated with Epileptic encephalopathy (ClinVar).

How common is FASN p.Pro208= (c.624C>T) in the general population?

FASN p.Pro208= (c.624C>T) is low-frequency (popmax 2.1%, afr) (gnomAD).

FASN p.Pro208=

c.624C>T · rs45624241 · VCV462095

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.1%, afr)

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 -8.3	GERP -2.8
Overall
CADD	0.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.1% African / African-American · 1,569/74,758 alleles

Filtering AF 2.01% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.98%

Overall 0.108% 1,714/1,591,542 alleles · low-frequency exomes 831/1,439,212 · genomes 883/152,330 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.1%	48
Remaining individualsnot grpmax-eligible	0.0925%	1,082
Middle Eastern	0.0904%	1,106
Admixed American	0.0722%	1,385
South Asian	0.00569%	17,561
East Asian	0.00455%	21,967
European (non-Finnish)	0.00299%	33,427

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.Pro208=
Coding: c.624C>T
MANE Select: NM_004104
dbSNP: rs45624241
Type: single nucleotide variant
Location: chr17:82093250 (GRCh38)
Gene constraint: LOEUF 0.284 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.65 · 34 PDB
Residue 208: the ketosynthase family 3 (ks3) domain

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-pro208 (accessed [today's date]).

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