Is CMBL p.Ile113Val (c.337A>G) pathogenic?

CMBL p.Ile113Val (c.337A>G) is classified Likely benign in CMBL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-09). AlphaMissense: likely benign (0.068); Ultra-rare (popmax 0.0493%, mid).

How common is CMBL p.Ile113Val (c.337A>G) in the general population?

CMBL p.Ile113Val (c.337A>G) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

What do computational predictors say about CMBL p.Ile113Val (c.337A>G)?

AlphaMissense predicts likely benign (score 0.068) — an in-silico prediction, not a clinical call.

CMBL p.Ile113Val

c.337A>G · rs372248737 · VCV3146204

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.068 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.068	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -3.72	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 1.6	GERP 1.5, phastCons 0.88
Regional constraint	o/e 1.04	unconstrained · MANE · 10 kb · p 0.51 · regional, not allelic
Overall
CADD	3.898	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 0.0493% Middle Eastern · 3/6,084 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00715%

Overall 0.000682% 11/1,613,954 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,028
African / African-American	0.00133%	74,936
South Asian	0.0011%	91,040
European (non-Finnish)	0.000508%	196,662

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: CMBL
Protein: p.Ile113Val
Coding: c.337A>G
MANE Select: NM_138809
dbSNP: rs372248737
Type: single nucleotide variant
Location: chr5:10286483 (GRCh38)
Gene constraint: LOEUF 0.781 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 91.92

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

Similar variants

CMBL p.Asn178= Benign ★★ same type
CMBL p.Gln192Ter Benign ★★ same type
CMBL p.Ala63Pro Uncertain significance ★ ⚠ same type
CMBL p.Arg101Gly Uncertain significance ★ ⚠ same type
CMBL p.Arg101Ile Uncertain significance ★ ⚠ same type
CMBL p.Arg217Gln Uncertain significance ★ ⚠ same type
CMBL p.Arg23Cys Uncertain significance ★ ⚠ same type
CMBL p.Arg23Gly 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/cmbl-p-ile113val (accessed [today's date]).

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