Is CPED1 p.Thr125Met (c.374C>T) pathogenic?

CPED1 p.Thr125Met (c.374C>T) is classified Uncertain significance in CPED1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-09). AlphaMissense: likely benign (0.0913); Ultra-rare (popmax 0.0673%, amr).

How common is CPED1 p.Thr125Met (c.374C>T) in the general population?

CPED1 p.Thr125Met (c.374C>T) is ultra-rare (popmax 0.0673%, amr) (gnomAD).

What do computational predictors say about CPED1 p.Thr125Met (c.374C>T)?

AlphaMissense predicts likely benign (score 0.0913) — an in-silico prediction, not a clinical call.

CPED1 p.Thr125Met

c.374C>T · rs752999333 · VCV2350431

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0913 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0673%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0913	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -8.69	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 -1.7	GERP 4.1
Regional constraint	o/e 1.00	unconstrained · MANE · 306 kb · p 0.91 · regional, not allelic
Overall
CADD	14.02	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 0.0673% Admixed American · 38/56,504 alleles

Filtering AF 0.0503% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0444%

Overall 0.00443% 71/1,601,606 alleles · ultra-rare exomes 68/1,449,396 · genomes 3/152,210 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0673%	1,487
Middle Eastern	0.0165%	6,052
Ashkenazi Jewishnot grpmax-eligible	0.00342%	29,230
South Asian	0.0034%	29,427
European (non-Finnish)	0.0023%	43,565
African / African-American	0.00135%	74,090

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: CPED1
Protein: p.Thr125Met
Coding: c.374C>T
MANE Select: NM_024913
dbSNP: rs752999333
Type: single nucleotide variant
Location: chr7:121015789 (GRCh38)
Gene constraint: LOEUF 1.142 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.08

Full CPED1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPED1 c.2634-3C>A Benign ★★ same type
CPED1 p.Gly140= Benign ★★ same type
CPED1 p.Lys949Thr Benign ★★ same type
CPED1 p.Thr293= Benign ★★ same type
CPED1 p.Ala43Pro Uncertain significance ★ ⚠ same type
CPED1 p.Ala44Gly Uncertain significance ★ ⚠ same type
CPED1 p.Ala652Val Uncertain significance ★ ⚠ same type
CPED1 p.Arg1018Ser 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/cped1-p-thr125met (accessed [today's date]).

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