Is ATG2B p.Phe826Val (c.2476T>G) pathogenic?

ATG2B p.Phe826Val (c.2476T>G) is classified Uncertain significance in ATG2B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). AlphaMissense: likely benign (0.2243); Very rare (popmax 8.48e-05%, nfe).

How common is ATG2B p.Phe826Val (c.2476T>G) in the general population?

ATG2B p.Phe826Val (c.2476T>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about ATG2B p.Phe826Val (c.2476T>G)?

AlphaMissense predicts likely benign (score 0.2243) — an in-silico prediction, not a clinical call.

ATG2B p.Phe826Val

c.2476T>G · VCV3443623

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2243 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2243	likely benign
REVEL	0.395	indeterminate
SaProt	LLR -7.86	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 61 kb · p 0.06 · regional, not allelic
Overall
CADD	25.8	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 8.48e-05% European (non-Finnish) · 1/1,179,094 alleles

Overall 6.21e-05% 1/1,610,732 alleles · very rare exomes 1/1,458,548 · genomes 0/152,184 · joint denominator

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: ATG2B
Protein: p.Phe826Val
Coding: c.2476T>G
MANE Select: NM_018036
Type: single nucleotide variant
Location: chr14:96323960 (GRCh38)
Gene constraint: LOEUF 0.586 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.72

Full ATG2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATG2B c.163-25T>A Benign ★★ same type
ATG2B c.163-39G>C Benign ★★ same type
ATG2B c.1731-26C>G Benign ★★ same type
ATG2B c.3038-73T>A Benign ★★ same type
ATG2B c.3210+18G>A Benign ★★ same type
ATG2B c.3210+66C>T Benign ★★ same type
ATG2B c.3362-4C>G Benign ★★ same type
ATG2B c.3643-123T>C Benign ★★ 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/atg2b-p-phe826val (accessed [today's date]).

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