Is CMIP p.Ile605Val (c.1813A>G) pathogenic?

CMIP p.Ile605Val (c.1813A>G) is classified Uncertain significance in CMIP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-29). AlphaMissense: likely benign (0.2565); Very rare (popmax 0.00873%, nfe).

How common is CMIP p.Ile605Val (c.1813A>G) in the general population?

CMIP p.Ile605Val (c.1813A>G) is very rare (popmax 0.00873%, nfe) (gnomAD).

What do computational predictors say about CMIP p.Ile605Val (c.1813A>G)?

AlphaMissense predicts likely benign (score 0.2565) — an in-silico prediction, not a clinical call.

CMIP p.Ile605Val

c.1813A>G · rs369298377 · VCV2515032

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2565 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00873%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2565	likely benign
REVEL	0.267	benign-leaning
SaProt	LLR -6.05	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.24	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 18 kb · p 1.7e-09 · regional, not allelic
Overall
CADD	24.7	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 0.00873% European (non-Finnish) · 103/1,179,898 alleles

Filtering AF 0.00733% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00684%

Overall 0.00638% 103/1,613,830 alleles · very rare

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: CMIP
Protein: p.Ile605Val
Coding: c.1813A>G
MANE Select: NM_198390
dbSNP: rs369298377
Type: single nucleotide variant
Location: chr16:81701717 (GRCh38)
Gene constraint: LOEUF 0.189 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.52

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

Similar variants

CMIP c.1638+10G>A Likely benign ★★ same type
CMIP c.2269-10C>T Benign/Likely benign ★★ same type
CMIP p.Asn295= Benign ★★ same type
CMIP p.Leu369= Likely benign ★★ same type
CMIP p.Pro414= Benign ★★ same type
CMIP p.Val547= Benign ★★ same type
CMIP c.1035-1G>A Uncertain significance ★ same type
CMIP p.Ala113Thr 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/cmip-p-ile605val (accessed [today's date]).

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