Is ATG2A p.Val1237Ile (c.3709G>A) pathogenic?

ATG2A p.Val1237Ile (c.3709G>A) is classified Uncertain significance in ATG2A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-17). AlphaMissense: likely benign (0.0747); Ultra-rare (popmax 0.0507%, afr).

How common is ATG2A p.Val1237Ile (c.3709G>A) in the general population?

ATG2A p.Val1237Ile (c.3709G>A) is ultra-rare (popmax 0.0507%, afr) (gnomAD).

What do computational predictors say about ATG2A p.Val1237Ile (c.3709G>A)?

AlphaMissense predicts likely benign (score 0.0747) — an in-silico prediction, not a clinical call.

ATG2A p.Val1237Ile

c.3709G>A · rs145632022 · VCV2352926

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0747 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0507%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0747	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	LLR -5.94	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.65	donor loss, 5 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -0.42	GERP -3.2
Regional constraint	o/e 0.88	unconstrained · MANE · 22 kb · p 3.8e-09 · regional, not allelic
Overall
CADD	14.91	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 0.0507% African / African-American · 38/74,888 alleles

Filtering AF 0.038% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0335%

Overall 0.00342% 55/1,606,082 alleles · ultra-rare exomes 31/1,453,842 · genomes 24/152,240 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0507%	1,971
Middle Eastern	0.0221%	4,522
Remaining individualsnot grpmax-eligible	0.00644%	15,529
Admixed American	0.00168%	59,564
European (non-Finnish)	0.000934%	107,090

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: ATG2A
Protein: p.Val1237Ile
Coding: c.3709G>A
MANE Select: NM_015104
dbSNP: rs145632022
Type: single nucleotide variant
Location: chr11:64902584 (GRCh38)
Gene constraint: LOEUF 0.614 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.38 · 7 PDB

Full ATG2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATG2A p.Ala857Val Benign ★★ same type
ATG2A p.Pro291= Benign ★★ same type
ATG2A p.Val1825Ile Benign ★★ same type
ATG2A p.Val664Met Benign ★★ same type
ATG2A p.Ala1033Gly Uncertain significance ★ ⚠ same type
ATG2A p.Ala1162Val Uncertain significance ★ same type
ATG2A p.Ala1367Val Uncertain significance ★ ⚠ same type
ATG2A p.Ala1505Glu 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/atg2a-p-val1237ile (accessed [today's date]).

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