Is IMP4 p.Arg48Gln (c.143G>A) pathogenic?

IMP4 p.Arg48Gln (c.143G>A) is classified Uncertain significance in IMP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-26). AlphaMissense: likely benign (0.0849); Ultra-rare (popmax 0.033%, mid).

How common is IMP4 p.Arg48Gln (c.143G>A) in the general population?

IMP4 p.Arg48Gln (c.143G>A) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about IMP4 p.Arg48Gln (c.143G>A)?

AlphaMissense predicts likely benign (score 0.0849) — an in-silico prediction, not a clinical call.

IMP4 p.Arg48Gln

c.143G>A · rs34815785 · VCV2227812

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0849 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0849	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -8.29	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 0.5	phastCons 0.21
Regional constraint	o/e 0.93	unconstrained · MANE · 3,532 bp · p 0.15 · regional, not allelic
Overall
CADD	17.9	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 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.0209% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0178%

Overall 0.0143% 231/1,614,102 alleles · ultra-rare exomes 199/1,461,782 · genomes 32/152,320 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
African / African-American	0.0307%	3,263
Admixed American	0.0267%	3,752
Remaining individualsnot grpmax-eligible	0.024%	4,167
European (non-Finnish)	0.0146%	6,860
Finnishnot grpmax-eligible	0.00312%	32,017
South Asian	0.0011%	91,086

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.Arg48Gln
Coding: c.143G>A
MANE Select: NM_033416
dbSNP: rs34815785
Type: single nucleotide variant
Location: chr2:130344659 (GRCh38)
Gene constraint: LOEUF 1.064 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.47 · 3 PDB
Residue 48: an α-helix

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-arg48gln (accessed [today's date]).

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