Is CMBL p.Ser37Phe (c.110C>T) pathogenic?

CMBL p.Ser37Phe (c.110C>T) is classified Uncertain significance in CMBL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-10). AlphaMissense: ambiguous (0.4461); Absent from gnomAD v4.1.

How common is CMBL p.Ser37Phe (c.110C>T) in the general population?

CMBL p.Ser37Phe (c.110C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CMBL p.Ser37Phe (c.110C>T)?

AlphaMissense predicts ambiguous (score 0.4461) — an in-silico prediction, not a clinical call.

CMBL p.Ser37Phe

c.110C>T · VCV4004004

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4461 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4461	ambiguous
REVEL	0.206	benign-leaning
SaProt	LLR -13.19	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP -0.33, phastCons 0.97
Regional constraint	o/e 1.04	unconstrained · MANE · 10 kb · p 0.51 · regional, not allelic
Overall
CADD	23.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CMBL
Protein: p.Ser37Phe
Coding: c.110C>T
MANE Select: NM_138809
Type: single nucleotide variant
Location: chr5:10290653 (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-ser37phe (accessed [today's date]).

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