Is AFG2B p.Val501Ala (c.1502T>C) pathogenic?

AFG2B p.Val501Ala (c.1502T>C) is classified Uncertain significance in AFG2B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-16). AlphaMissense: ambiguous (0.4205); Very rare (popmax 0.000254%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AFG2B p.Val501Ala (c.1502T>C)?

AFG2B p.Val501Ala (c.1502T>C) is associated with Inborn genetic diseases (ClinVar).

How common is AFG2B p.Val501Ala (c.1502T>C) in the general population?

AFG2B p.Val501Ala (c.1502T>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about AFG2B p.Val501Ala (c.1502T>C)?

AlphaMissense predicts ambiguous (score 0.4205) — an in-silico prediction, not a clinical call.

AFG2B p.Val501Ala

c.1502T>C · rs2542067616 · VCV2245519

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4205 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4205	ambiguous
REVEL	0.734	pathogenic-leaning
SaProt	LLR -10.43	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 19 kb · p 0.58 · regional, not allelic
Overall
CADD	25.1	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 0.000254% European (non-Finnish) · 3/1,179,998 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,864 alleles · very rare

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.Val501Ala
Coding: c.1502T>C
MANE Select: NM_024063
dbSNP: rs2542067616
Type: single nucleotide variant
Location: chr15:45414638 (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.Val501Phe 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.Ala130Thr Uncertain significance ★ ⚠ same condition
AFG2B p.Ala130Val Uncertain significance ★ ⚠ same condition
AFG2B p.Ala135Thr 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-val501ala (accessed [today's date]).

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