Is CPM p.Leu210Ser (c.629T>C) pathogenic?

CPM p.Leu210Ser (c.629T>C) is classified Uncertain significance in CPM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-23). AlphaMissense: likely benign (0.0814); Ultra-rare (popmax 0.0134%, nfe).

How common is CPM p.Leu210Ser (c.629T>C) in the general population?

CPM p.Leu210Ser (c.629T>C) is ultra-rare (popmax 0.0134%, nfe) (gnomAD).

What do computational predictors say about CPM p.Leu210Ser (c.629T>C)?

AlphaMissense predicts likely benign (score 0.0814) — an in-silico prediction, not a clinical call.

CPM p.Leu210Ser

c.629T>C · VCV3835897

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0814 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0814	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -3.93	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 0.88	GERP -0.65
Regional constraint	o/e 0.80	unconstrained · MANE · 76 kb · p 2.5e-06 · regional, not allelic
Overall
CADD	4.844	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 0.0134% European (non-Finnish) · 157/1,175,396 alleles

Filtering AF 0.0116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.011%

Overall 0.0103% 165/1,605,886 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0134%	7,487
Remaining individualsnot grpmax-eligible	0.00805%	12,427
African / African-American	0.00269%	37,224
Admixed American	0.00171%	58,596

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: CPM
Protein: p.Leu210Ser
Coding: c.629T>C
MANE Select: NM_198320
Type: single nucleotide variant
Location: chr12:68869483 (GRCh38)
Gene constraint: LOEUF 1.017 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.49 · 1 PDB
Residue 210: a disulfide bond; the peptidase m14 domain; an α-helix

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

Similar variants

CPM p.Ala209Ser Uncertain significance ★ ⚠ same type
CPM p.Ala36Thr Uncertain significance ★ ⚠ same type
CPM p.Arg118Gln Uncertain significance ★ ⚠ same type
CPM p.Arg213Gln Uncertain significance ★ ⚠ same type
CPM p.Arg289Cys Uncertain significance ★ ⚠ same type
CPM p.Arg289Gly Uncertain significance ★ ⚠ same type
CPM p.Arg289His Uncertain significance ★ ⚠ same type
CPM p.Asn299Ser 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/cpm-p-leu210ser (accessed [today's date]).

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