Is AIMP2 p.Ser134Phe (c.401C>T) pathogenic?

AIMP2 p.Ser134Phe (c.401C>T) is classified Uncertain significance in AIMP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-17). AlphaMissense: likely pathogenic (0.7128); Ultra-rare (popmax 0.0567%, amr).

How common is AIMP2 p.Ser134Phe (c.401C>T) in the general population?

AIMP2 p.Ser134Phe (c.401C>T) is ultra-rare (popmax 0.0567%, amr) (gnomAD).

What do computational predictors say about AIMP2 p.Ser134Phe (c.401C>T)?

AlphaMissense predicts likely pathogenic (score 0.7128) — an in-silico prediction, not a clinical call.

AIMP2 p.Ser134Phe

c.401C>T · rs769933568 · VCV2189420

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7128 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0567%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7128	likely pathogenic
REVEL	0.414	indeterminate
SaProt	LLR -9.85	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	phastCons 1
Regional constraint	o/e 1.24	unconstrained · MANE · 14 kb · p 8e-07 · regional, not allelic
Overall
CADD	24.2	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 0.0567% Admixed American · 34/59,974 alleles

Filtering AF 0.0417% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0365%

Overall 0.00229% 37/1,614,026 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0567%	1,764
Remaining individualsnot grpmax-eligible	0.0032%	31,243
East Asian	0.00223%	44,888

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: AIMP2
Protein: p.Ser134Phe
Coding: c.401C>T
MANE Select: NM_006303
dbSNP: rs769933568
Type: single nucleotide variant
Location: chr7:6017872 (GRCh38)
Gene constraint: LOEUF 1.107 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.65 · 13 PDB
Residue 134: the 'interaction with prkn' region; an α-helix; a UniProt-annotated variant site (in hld17)

Full AIMP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AIMP2 p.Ser134= Likely benign ★ same residue
PMS2 c.-2146C>A Benign ★★★ same type
PMS2 c.-2559T>A Benign ★★★ same type
PMS2 c.-323G>T Benign ★★★ same type
AIMP2 p.Tyr35Ter Likely pathogenic ★★ same type
AIMP2 p.Ala240Val Uncertain significance ★★ ⚠ same type
AIMP2 p.Arg215Cys Uncertain significance ★★ ⚠ same type
AIMP2 p.Arg215His Uncertain significance ★★ ⚠ 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/aimp2-p-ser134phe (accessed [today's date]).

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