Is IMP4 p.Val247Ile (c.739G>A) pathogenic?

IMP4 p.Val247Ile (c.739G>A) is classified Uncertain significance in IMP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-13). AlphaMissense: likely benign (0.1102); Ultra-rare (popmax 0.0329%, mid).

How common is IMP4 p.Val247Ile (c.739G>A) in the general population?

IMP4 p.Val247Ile (c.739G>A) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about IMP4 p.Val247Ile (c.739G>A)?

AlphaMissense predicts likely benign (score 0.1102) — an in-silico prediction, not a clinical call.

IMP4 p.Val247Ile

c.739G>A · rs776773967 · VCV2301457

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1102 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1102	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -5.11	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 12	phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 3,532 bp · p 0.15 · regional, not allelic
Overall
CADD	22.1	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 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00275%

Overall 0.00335% 54/1,614,044 alleles · ultra-rare exomes 51/1,461,890 · genomes 3/152,154 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
Remaining individualsnot grpmax-eligible	0.0048%	20,829
European (non-Finnish)	0.00398%	25,107
South Asian	0.0022%	45,539

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: IMP4
Protein: p.Val247Ile
Coding: c.739G>A
MANE Select: NM_033416
dbSNP: rs776773967
Type: single nucleotide variant
Location: chr2:130346250 (GRCh38)
Gene constraint: LOEUF 1.064 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.47 · 3 PDB
Residue 247: the brix domain

Full IMP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

IMP4 p.Ala21Val Uncertain significance ★ ⚠ same type
IMP4 p.Ala282Thr Uncertain significance ★ ⚠ same type
IMP4 p.Arg126Gln Uncertain significance ★ ⚠ same type
IMP4 p.Arg170Trp Uncertain significance ★ ⚠ same type
IMP4 p.Arg194Cys Uncertain significance ★ ⚠ same type
IMP4 p.Arg198Gln Uncertain significance ★ ⚠ same type
IMP4 p.Arg204Gln Uncertain significance ★ ⚠ same type
IMP4 p.Arg216Gln 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/imp4-p-val247ile (accessed [today's date]).

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