Is AFG2B p.Ala307Pro (c.919G>C) pathogenic?

AFG2B p.Ala307Pro (c.919G>C) is classified Uncertain significance in AFG2B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). AlphaMissense: likely pathogenic (0.7411); Very rare (popmax 0.000764%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AFG2B p.Ala307Pro (c.919G>C)?

AFG2B p.Ala307Pro (c.919G>C) is associated with Inborn genetic diseases (ClinVar).

How common is AFG2B p.Ala307Pro (c.919G>C) in the general population?

AFG2B p.Ala307Pro (c.919G>C) is very rare (popmax 0.000764%, nfe) (gnomAD).

What do computational predictors say about AFG2B p.Ala307Pro (c.919G>C)?

AlphaMissense predicts likely pathogenic (score 0.7411) — an in-silico prediction, not a clinical call.

AFG2B p.Ala307Pro

c.919G>C · rs777840398 · VCV3093074

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7411 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000764%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7411	likely pathogenic
REVEL	0.568	indeterminate
SaProt	LLR -11.79	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 0.3, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 19 kb · p 0.58 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.000764% European (non-Finnish) · 9/1,178,190 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.00292% 47/1,608,208 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0545%	1,834
Remaining individualsnot grpmax-eligible	0.00643%	15,557
European (non-Finnish)grpmax	0.000764%	130,910

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.Ala307Pro
Coding: c.919G>C
MANE Select: NM_024063
dbSNP: rs777840398
Type: single nucleotide variant
Location: chr15:45403348 (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-ala307pro (accessed [today's date]).

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