Is CACHD1 p.Arg837= (c.2511G>A) pathogenic?

CACHD1 p.Arg837= (c.2511G>A) is classified Likely benign in CACHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-08). Ultra-rare (popmax 0.0813%, sas); Associated with Inborn genetic diseases.

What condition is associated with CACHD1 p.Arg837= (c.2511G>A)?

CACHD1 p.Arg837= (c.2511G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CACHD1 p.Arg837= (c.2511G>A) in the general population?

CACHD1 p.Arg837= (c.2511G>A) is ultra-rare (popmax 0.0813%, sas) (gnomAD).

CACHD1 p.Arg837=

c.2511G>A · rs536529670 · VCV3136287

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0813%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP -1, phastCons 1
Overall
CADD	14.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0813% South Asian · 74/91,014 alleles

Filtering AF 0.0664% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0609%

Overall 0.00583% 94/1,612,612 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0813%	1,230
Remaining individualsnot grpmax-eligible	0.0208%	4,801
East Asian	0.0156%	6,407

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.Arg837=
Coding: c.2511G>A
MANE Select: NM_020925
dbSNP: rs536529670
Type: single nucleotide variant
Location: chr1:64673158 (GRCh38)
Gene constraint: LOEUF 0.633 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.76
Residue 837: the cache 2 domain

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-arg837 (accessed [today's date]).

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