Is AFG2A p.Ile172fs (c.513del) pathogenic?

AFG2A p.Ile172fs (c.513del) is classified Likely pathogenic in AFG2A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-21). Very rare (popmax 0.000257%, nfe); Associated with AFG2A-related disorder.

What condition is associated with AFG2A p.Ile172fs (c.513del)?

AFG2A p.Ile172fs (c.513del) is associated with AFG2A-related disorder (ClinVar).

How common is AFG2A p.Ile172fs (c.513del) in the general population?

AFG2A p.Ile172fs (c.513del) is very rare (popmax 0.000257%, nfe) (gnomAD).

AFG2A p.Ile172fs

c.513del · rs1423563495 · VCV2630298

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000257%, nfe)

Conditions

AFG2A-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.1	GERP 1.6, phastCons 1
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000257% European (non-Finnish) · 3/1,165,838 alleles

Filtering AF 6.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000189% 3/1,590,120 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: AFG2A
Protein: p.Ile172fs
Coding: c.513del
MANE Select: NM_145207
dbSNP: rs1423563495
Type: Deletion
Location: chr4:122934104 (GRCh38)
Structure: AlphaFold pLDDT 73.21 · 2 PDB
Residue 172: the 'required for interaction with afg2b and cinp' region; a UniProt-annotated variant site (in nedhsb)

Full AFG2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

AFG2A-related disorder

Similar variants

AFG2A c.1147+1_1147+5del Likely pathogenic ★★ same condition
AFG2A c.1714+1G>A Pathogenic ★★ same condition
AFG2A p.Arg445Ter Pathogenic/Likely pathogenic ★★ same condition
AFG2A p.Gln132Ter Pathogenic ★★ same condition
AFG2A p.Arg714Ter Conflicting classifications of pathogenicity ★ same condition
AFG2A p.Arg124Ser Uncertain significance ⚠ same condition
AFG2A p.Ala742fs Pathogenic/Likely pathogenic ★★ same type
AFG2A p.Asn525fs Pathogenic ★★ same type

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/afg2a-p-ile172fs (accessed [today's date]).

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