Is CPPED1 p.Glu137Val (c.410A>T) pathogenic?

CPPED1 p.Glu137Val (c.410A>T) is classified Uncertain significance in CPPED1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: likely benign (0.1767); Ultra-rare (popmax 0.0111%, eas).

How common is CPPED1 p.Glu137Val (c.410A>T) in the general population?

CPPED1 p.Glu137Val (c.410A>T) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about CPPED1 p.Glu137Val (c.410A>T)?

AlphaMissense predicts likely benign (score 0.1767) — an in-silico prediction, not a clinical call.

CPPED1 p.Glu137Val

c.410A>T · rs775720619 · VCV3076826

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1767 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1767	likely benign
REVEL	0.532	indeterminate
SaProt	LLR -10.78	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 4.9, phastCons 1
Regional constraint	o/e 1.21	unconstrained · MANE · 139 kb · p 1.8e-05 · regional, not allelic
Overall
CADD	22.7	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 0.0111% East Asian · 5/44,880 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.000342% 5/1,461,894 alleles · ultra-rare

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: CPPED1
Protein: p.Glu137Val
Coding: c.410A>T
MANE Select: NM_018340
dbSNP: rs775720619
Type: single nucleotide variant
Location: chr16:12704929 (GRCh38)
Gene constraint: LOEUF 1.288 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.46
Residue 137: the 'catalytic' region

Full CPPED1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPPED1 p.Ala118Ser Uncertain significance ★ ⚠ same type
CPPED1 p.Ala192Val Uncertain significance ★ ⚠ same type
CPPED1 p.Ala200Thr Uncertain significance ★ ⚠ same type
CPPED1 p.Ala20Gly Uncertain significance ★ ⚠ same type
CPPED1 p.Ala20Pro Uncertain significance ★ ⚠ same type
CPPED1 p.Ala20Thr Uncertain significance ★ ⚠ same type
CPPED1 p.Ala238Thr Uncertain significance ★ ⚠ same type
CPPED1 p.Ala3Val 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/cpped1-p-glu137val (accessed [today's date]).

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