Is AFG2B p.Ala289Ser (c.865G>T) pathogenic?

AFG2B p.Ala289Ser (c.865G>T) is classified Uncertain significance in AFG2B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-03). AlphaMissense: likely benign (0.1931); Very rare (popmax 0.00231%, eas); Associated with Inborn genetic diseases.

What condition is associated with AFG2B p.Ala289Ser (c.865G>T)?

AFG2B p.Ala289Ser (c.865G>T) is associated with Inborn genetic diseases (ClinVar).

How common is AFG2B p.Ala289Ser (c.865G>T) in the general population?

AFG2B p.Ala289Ser (c.865G>T) is very rare (popmax 0.00231%, eas) (gnomAD).

What do computational predictors say about AFG2B p.Ala289Ser (c.865G>T)?

AlphaMissense predicts likely benign (score 0.1931) — an in-silico prediction, not a clinical call.

AFG2B p.Ala289Ser

c.865G>T · rs1595494243 · VCV3093064

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1931 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00231%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1931	likely benign
REVEL	0.833	moderately pathogenic-leaning
SaProt	LLR -10.04	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.3, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 19 kb · p 0.58 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00231% East Asian · 1/43,260 alleles

Overall 0.000209% 3/1,436,924 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00231%	43,260
Finnishnot grpmax-eligible	0.00168%	59,574
European (non-Finnish)	8.55e-05%	1,169,613

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: AFG2B
Protein: p.Ala289Ser
Coding: c.865G>T
MANE Select: NM_024063
dbSNP: rs1595494243
Type: single nucleotide variant
Location: chr15:45403294 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 2 PDB

Full AFG2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AFG2B p.Arg28Cys Uncertain significance ★★ ⚠ same condition
AFG2B p.Pro558Arg Uncertain significance ★★ ⚠ same condition
AFG2B p.Ser333Ile Uncertain significance ★★ ⚠ same condition
AFG2B p.Tyr738Cys Uncertain significance ★★ ⚠ same condition
AFG2B p.Ala130Thr Uncertain significance ★ ⚠ same condition
AFG2B p.Ala130Val Uncertain significance ★ ⚠ same condition
AFG2B p.Ala135Thr Uncertain significance ★ ⚠ same condition
AFG2B p.Ala156Ser 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/afg2b-p-ala289ser (accessed [today's date]).

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