Is CACHD1 p.Pro1010Ser (c.3028C>T) pathogenic?

CACHD1 p.Pro1010Ser (c.3028C>T) is classified Uncertain significance in CACHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-29). AlphaMissense: likely benign (0.0682); Rare (popmax 0.147%, afr); Associated with Inborn genetic diseases.

What condition is associated with CACHD1 p.Pro1010Ser (c.3028C>T)?

CACHD1 p.Pro1010Ser (c.3028C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CACHD1 p.Pro1010Ser (c.3028C>T) in the general population?

CACHD1 p.Pro1010Ser (c.3028C>T) is rare (popmax 0.147%, afr) (gnomAD).

What do computational predictors say about CACHD1 p.Pro1010Ser (c.3028C>T)?

AlphaMissense predicts likely benign (score 0.0682) — an in-silico prediction, not a clinical call.

CACHD1 p.Pro1010Ser

c.3028C>T · VCV3483899

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0682 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.147%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0682	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -7.31	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 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 6,155 bp · p 0.012 · regional, not allelic
Overall
CADD	19.83	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 0.147% African / African-American · 110/75,028 alleles

Filtering AF 0.124% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.116%

Overall 0.0075% 121/1,614,006 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.147%	682
Remaining individualsnot grpmax-eligible	0.0128%	7,813
Admixed American	0.00333%	30,003
European (non-Finnish)	8.48e-05%	1,179,940

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: CACHD1
Protein: p.Pro1010Ser
Coding: c.3028C>T
MANE Select: NM_020925
Type: single nucleotide variant
Location: chr1:64676947 (GRCh38)
Gene constraint: LOEUF 0.633 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.76

Full CACHD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CACHD1 p.Ala1058Val Uncertain significance ★ ⚠ same condition
CACHD1 p.Ala1113Val Uncertain significance ★ ⚠ same condition
CACHD1 p.Ala116Thr Uncertain significance ★ ⚠ same condition
CACHD1 p.Ala1170Thr Uncertain significance ★ ⚠ same condition
CACHD1 p.Ala1263Val Uncertain significance ★ ⚠ same condition
CACHD1 p.Ala257Thr Uncertain significance ★ ⚠ same condition
CACHD1 p.Ala314Thr Uncertain significance ★ ⚠ same condition
CACHD1 p.Ala314Val Uncertain significance ★ ⚠ same condition

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/cachd1-p-pro1010ser (accessed [today's date]).

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