Is AGER p.Ile30Val (c.88A>G) pathogenic?

AGER p.Ile30Val (c.88A>G) is classified Uncertain significance in AGER (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-29). AlphaMissense: likely benign (0.1338); Very rare (popmax 0.00267%, afr).

How common is AGER p.Ile30Val (c.88A>G) in the general population?

AGER p.Ile30Val (c.88A>G) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about AGER p.Ile30Val (c.88A>G)?

AlphaMissense predicts likely benign (score 0.1338) — an in-silico prediction, not a clinical call.

AGER p.Ile30Val

c.88A>G · rs1034066092 · VCV2359551

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1338 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1338	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -4.73	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.26	loss · gain 0.02 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 5	GERP -0.22, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 3,076 bp · p 0.25 · regional, not allelic
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00267% African / African-American · 2/74,880 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,612,842 alleles · very rare exomes 0/1,460,752 · genomes 2/152,090 · joint denominator

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: AGER
Protein: p.Ile30Val
Coding: c.88A>G
MANE Select: NM_001136
dbSNP: rs1034066092
Type: single nucleotide variant
Location: chr6:32183952 (GRCh38)
Gene constraint: LOEUF 1.068 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.74 · 33 PDB
Residue 30: the ig-like v-type domain

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

Similar variants

AGER p.Ala19Gly Uncertain significance ★ ⚠ same type
AGER p.Ala355Thr Uncertain significance ★ ⚠ same type
AGER p.Ala375Ser Uncertain significance ★ ⚠ same type
AGER p.Ala41Val Uncertain significance ★ ⚠ same type
AGER p.Ala6Val Uncertain significance ★ ⚠ same type
AGER p.Ala76Val Uncertain significance ★ ⚠ same type
AGER p.Arg116Leu Uncertain significance ★ ⚠ same type
AGER p.Arg178Ser 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/ager-p-ile30val (accessed [today's date]).

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