Is AFG3L2 p.Pro610Ala (c.1828C>G) pathogenic?

AFG3L2 p.Pro610Ala (c.1828C>G) is classified Uncertain significance in AFG3L2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-20). AlphaMissense: likely pathogenic (0.9687); Ultra-rare (popmax 0.0174%, afr); Associated with Inborn genetic diseases.

What condition is associated with AFG3L2 p.Pro610Ala (c.1828C>G)?

AFG3L2 p.Pro610Ala (c.1828C>G) is associated with Inborn genetic diseases (ClinVar).

How common is AFG3L2 p.Pro610Ala (c.1828C>G) in the general population?

AFG3L2 p.Pro610Ala (c.1828C>G) is ultra-rare (popmax 0.0174%, afr) (gnomAD).

What do computational predictors say about AFG3L2 p.Pro610Ala (c.1828C>G)?

AlphaMissense predicts likely pathogenic (score 0.9687) — an in-silico prediction, not a clinical call.

AFG3L2 p.Pro610Ala

c.1828C>G · rs143133676 · VCV2230134

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9687 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9687	likely pathogenic
REVEL	0.818	moderately pathogenic-leaning
SaProt	LLR -16.96	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 22 kb · p 3e-07 · regional, not allelic
Overall
CADD	26.4	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 0.0174% African / African-American · 13/74,916 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00813%

Overall 0.000867% 14/1,614,022 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0174%	5,763
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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: AFG3L2
Protein: p.Pro610Ala
Coding: c.1828C>G
MANE Select: NM_006796
dbSNP: rs143133676
Type: single nucleotide variant
Location: chr18:12340353 (GRCh38)
Gene constraint: LOEUF 0.724 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.07 · 2 PDB

Full AFG3L2 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

AFG3L2 c.1318+6T>A Uncertain significance ★★ same condition
AFG3L2 p.Ala579Val Uncertain significance ★★ ⚠ same condition
AFG3L2 p.Ala751Val Uncertain significance ★★ ⚠ same condition
AFG3L2 p.Arg106His Uncertain significance ★★ ⚠ same condition
AFG3L2 p.Arg11Gly Uncertain significance ★★ ⚠ same condition
AFG3L2 p.Arg492Gln Uncertain significance ★★ ⚠ same condition
AFG3L2 p.Arg783Gln Uncertain significance ★★ ⚠ same condition
AFG3L2 p.Asn52Ser 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/afg3l2-p-pro610ala (accessed [today's date]).

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