Is CPED1 p.Ser671Arg (c.2011A>C) pathogenic?

CPED1 p.Ser671Arg (c.2011A>C) is classified Uncertain significance in CPED1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-25). AlphaMissense: likely pathogenic (0.8882); Very rare (popmax 0.000339%, nfe).

How common is CPED1 p.Ser671Arg (c.2011A>C) in the general population?

CPED1 p.Ser671Arg (c.2011A>C) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about CPED1 p.Ser671Arg (c.2011A>C)?

AlphaMissense predicts likely pathogenic (score 0.8882) — an in-silico prediction, not a clinical call.

CPED1 p.Ser671Arg

c.2011A>C · VCV3496400

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8882 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8882	likely pathogenic · top 6% in CPED1
REVEL	0.272	benign-leaning
SaProt	LLR -5.38	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 4, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 306 kb · p 0.91 · regional, not allelic
Overall
CADD	26.1	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 0.000339% European (non-Finnish) · 4/1,178,812 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,612,372 alleles · very rare exomes 4/1,460,174 · genomes 0/152,198 · joint denominator

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.Ser671Arg
Coding: c.2011A>C
MANE Select: NM_024913
Type: single nucleotide variant
Location: chr7:121142097 (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-ser671arg (accessed [today's date]).

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