Is CD37 p.Val123Leu (c.367G>T) pathogenic?

CD37 p.Val123Leu (c.367G>T) is classified Uncertain significance in CD37 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-17). AlphaMissense: ambiguous (0.4044); Very rare (popmax 0.00415%, nfe).

How common is CD37 p.Val123Leu (c.367G>T) in the general population?

CD37 p.Val123Leu (c.367G>T) is very rare (popmax 0.00415%, nfe) (gnomAD).

What do computational predictors say about CD37 p.Val123Leu (c.367G>T)?

AlphaMissense predicts ambiguous (score 0.4044) — an in-silico prediction, not a clinical call.

CD37 p.Val123Leu

c.367G>T · rs370552650 · VCV3140575

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4044 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00415%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4044	ambiguous
REVEL	0.507	indeterminate
SaProt	LLR -8.11	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 4,784 bp · p 0.63 · regional, not allelic
Overall
CADD	23.4	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 0.00415% European (non-Finnish) · 49/1,179,990 alleles

Filtering AF 0.00318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00286%

Overall 0.0031% 50/1,613,944 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00415%	24,081
African / African-American	0.00134%	74,890

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: CD37
Protein: p.Val123Leu
Coding: c.367G>T
MANE Select: NM_001774
dbSNP: rs370552650
Type: single nucleotide variant
Location: chr19:49337949 (GRCh38)
Gene constraint: LOEUF 1.215 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.31

Full CD37 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD37 p.Val44= Benign ★★ same type
CD37 p.Ala221Thr Uncertain significance ★ ⚠ same type
CD37 p.Arg112Gly Uncertain significance ★ ⚠ same type
CD37 p.Arg112Pro Uncertain significance ★ ⚠ same type
CD37 p.Arg120Leu Uncertain significance ★ ⚠ same type
CD37 p.Arg281Cys Uncertain significance ★ ⚠ same type
CD37 p.Arg281Ser Uncertain significance ★ ⚠ same type
CD37 p.Asn170Asp 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/cd37-p-val123leu (accessed [today's date]).

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