Is AIMP1 p.Pro79Ala (c.235C>G) pathogenic?

AIMP1 p.Pro79Ala (c.235C>G) is classified Benign in AIMP1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.0657); Common (popmax 26.2%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about AIMP1 p.Pro79Ala (c.235C>G)?

AlphaMissense predicts likely benign (score 0.0657) — an in-silico prediction, not a clinical call.

AIMP1 p.Pro79Ala

Q: How common is AIMP1 p.Pro79Ala (c.235C>G) in the general population?

AIMP1 p.Pro79Ala (c.235C>G) is common (popmax 26.2%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.235C>G · rs1134648 · VCV1166295

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0657 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 26.2%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0657	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -6.78	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 1.8, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 23 kb · p 0.91 · regional, not allelic
Overall
CADD	18.27	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 26.2% East Asian · 11,734/44,772 alleles

Filtering AF 25.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 25.6%

Overall 2.92% 47,080/1,612,366 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	26.2%	4
Admixed American	15.6%	6
South Asian	14%	7
Remaining individualsnot grpmax-eligible	3.8%	26
Finnishnot grpmax-eligible	1.95%	51
Ashkenazi Jewishnot grpmax-eligible	1.59%	63
Middle Eastern	0.975%	103
European (non-Finnish)	0.753%	133
African / African-American	0.399%	251

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: AIMP1
Protein: p.Pro79Ala
Coding: c.235C>G
MANE Select: NM_001142416
dbSNP: rs1134648
Type: single nucleotide variant
Location: chr4:106328087 (GRCh38)
Gene constraint: LOEUF 0.931 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 81.68 · 6 PDB
Residue 79: a UniProt-annotated variant site (in); the 'interaction with hsp90b1' region

Full AIMP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AIMP1 p.Gln112Ter Pathogenic ★★ same type
AIMP1 p.Gln39Ter Pathogenic/Likely pathogenic ★★ same type
AIMP1 c.773-2A>C Uncertain significance ★★ same type
AIMP1 p.Arg49Gln Uncertain significance ★★ ⚠ same type
AIMP1 p.Asn89Ser Uncertain significance ★★ ⚠ same type
AIMP1 p.Asp146Asn Uncertain significance ★★ ⚠ same type
AIMP1 p.Glu120Gly Uncertain significance ★★ ⚠ same type
AIMP1 p.Glu23Asp 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/aimp1-p-pro79ala (accessed [today's date]).

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