Is AFG2B p.Ala130Val (c.389C>T) pathogenic?

AFG2B p.Ala130Val (c.389C>T) is classified Uncertain significance in AFG2B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-14). AlphaMissense: likely benign (0.0879); Very rare (popmax 0.00017%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AFG2B p.Ala130Val (c.389C>T)?

AFG2B p.Ala130Val (c.389C>T) is associated with Inborn genetic diseases (ClinVar).

How common is AFG2B p.Ala130Val (c.389C>T) in the general population?

AFG2B p.Ala130Val (c.389C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about AFG2B p.Ala130Val (c.389C>T)?

AlphaMissense predicts likely benign (score 0.0879) — an in-silico prediction, not a clinical call.

AFG2B p.Ala130Val

c.389C>T · rs747960581 · VCV3093037

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0879 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0879	likely benign
REVEL	0.126	moderately benign-leaning
SaProt	LLR -6.58	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 -1.4	GERP -2.8
Regional constraint	o/e 0.98	unconstrained · MANE · 19 kb · p 0.58 · regional, not allelic
Overall
CADD	1.651	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 0.00017% European (non-Finnish) · 2/1,178,578 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000313% 5/1,596,846 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00601%	16,647
European (non-Finnish)grpmax	0.00017%	589,289

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala130Val
Coding: c.389C>T
MANE Select: NM_024063
dbSNP: rs747960581
Type: single nucleotide variant
Location: chr15:45402818 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 2 PDB
Residue 130: the 'required for interaction with afg2a and cinp' region

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.Ala130Thr Uncertain significance ★ ⚠ same residue
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.Ala135Thr Uncertain significance ★ ⚠ same condition
AFG2B p.Ala156Ser Uncertain significance ★ ⚠ same condition
AFG2B p.Ala225Val 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-ala130val (accessed [today's date]).

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