Is CD37 p.Asn275Lys (c.825C>A) pathogenic?

CD37 p.Asn275Lys (c.825C>A) is classified Uncertain significance in CD37 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-27). AlphaMissense: likely benign (0.2353); Ultra-rare (popmax 0.0133%, amr).

How common is CD37 p.Asn275Lys (c.825C>A) in the general population?

CD37 p.Asn275Lys (c.825C>A) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

What do computational predictors say about CD37 p.Asn275Lys (c.825C>A)?

AlphaMissense predicts likely benign (score 0.2353) — an in-silico prediction, not a clinical call.

CD37 p.Asn275Lys

c.825C>A · rs751006342 · VCV2389806

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2353 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2353	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -6.30	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 2.1	GERP 0.016, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 4,784 bp · p 0.63 · regional, not allelic
Overall
CADD	16.7	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 0.0133% Admixed American · 8/60,014 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.00211% 34/1,613,450 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,502
Remaining individualsnot grpmax-eligible	0.0032%	31,239
European (non-Finnish)	0.00203%	49,152

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.Asn275Lys
Coding: c.825C>A
MANE Select: NM_001774
dbSNP: rs751006342
Type: single nucleotide variant
Location: chr19:49340307 (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-asn275lys (accessed [today's date]).

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