Is FADS2 p.Glu413Asp (c.1239A>C) pathogenic?

FADS2 p.Glu413Asp (c.1239A>C) is classified Uncertain significance in FADS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-28). AlphaMissense: likely benign (0.0907); Very rare (popmax 0.00167%, amr).

How common is FADS2 p.Glu413Asp (c.1239A>C) in the general population?

FADS2 p.Glu413Asp (c.1239A>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about FADS2 p.Glu413Asp (c.1239A>C)?

AlphaMissense predicts likely benign (score 0.0907) — an in-silico prediction, not a clinical call.

FADS2 p.Glu413Asp

c.1239A>C · VCV4252524

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0907 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0907	likely benign
REVEL	0.01	strongly benign-leaning
SaProt	LLR -8.97	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 -0.62	GERP -1.4
Regional constraint	o/e 0.52	unconstrained · MANE · 25 kb · p 1.5e-23 · regional, not allelic
Overall
CADD	10.8	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 0.00167% Admixed American · 1/60,024 alleles

Overall 0.000186% 3/1,613,808 alleles · very rare exomes 3/1,461,480 · genomes 0/152,328 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,024
Remaining individualsnot grpmax-eligible	0.0016%	62,474
South Asian	0.0011%	91,076

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: FADS2
Protein: p.Glu413Asp
Coding: c.1239A>C
MANE Select: NM_004265
Type: single nucleotide variant
Location: chr11:61865233 (GRCh38)
Gene constraint: LOEUF 0.415 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 95.39

Full FADS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FADS2 p.His221= Benign ★★ same type
FADS2 p.Ala115Val Uncertain significance ★ ⚠ same type
FADS2 p.Ala408Ser Uncertain significance ★ ⚠ same type
FADS2 p.Arg14Cys Uncertain significance ★ ⚠ same type
FADS2 p.Arg353His Uncertain significance ★ ⚠ same type
FADS2 p.Arg58Gln Uncertain significance ★ ⚠ same type
FADS2 p.Arg73Cys Uncertain significance ★ ⚠ same type
FADS2 p.Asn156His Uncertain significance ★ ⚠ same type

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/fads2-p-glu413asp (accessed [today's date]).

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