Is AFG2B p.Pro430His (c.1289C>A) pathogenic?

AFG2B p.Pro430His (c.1289C>A) is classified Uncertain significance in AFG2B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-27). AlphaMissense: likely benign (0.1188); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with AFG2B p.Pro430His (c.1289C>A)?

AFG2B p.Pro430His (c.1289C>A) is associated with Inborn genetic diseases (ClinVar).

How common is AFG2B p.Pro430His (c.1289C>A) in the general population?

AFG2B p.Pro430His (c.1289C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AFG2B p.Pro430His (c.1289C>A)?

AlphaMissense predicts likely benign (score 0.1188) — an in-silico prediction, not a clinical call.

AFG2B p.Pro430His

c.1289C>A · rs2542059974 · VCV3092954

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1188 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1188	likely benign
REVEL	0.246	benign-leaning
SaProt	LLR -9.13	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 4	GERP 0.84, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 19 kb · p 0.58 · regional, not allelic
Overall
CADD	18.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AFG2B
Protein: p.Pro430His
Coding: c.1289C>A
MANE Select: NM_024063
dbSNP: rs2542059974
Type: single nucleotide variant
Location: chr15:45410385 (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-pro430his (accessed [today's date]).

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