Is CACHD1 p.Val62Phe (c.184G>T) pathogenic?

CACHD1 p.Val62Phe (c.184G>T) is classified Uncertain significance in CACHD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-10). AlphaMissense: likely benign (0.3349); Very rare (popmax 0.00204%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CACHD1 p.Val62Phe (c.184G>T)?

CACHD1 p.Val62Phe (c.184G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CACHD1 p.Val62Phe (c.184G>T) in the general population?

CACHD1 p.Val62Phe (c.184G>T) is very rare (popmax 0.00204%, nfe) (gnomAD).

What do computational predictors say about CACHD1 p.Val62Phe (c.184G>T)?

AlphaMissense predicts likely benign (score 0.3349) — an in-silico prediction, not a clinical call.

CACHD1 p.Val62Phe

c.184G>T · rs1270702988 · VCV2395796

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3349 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00204%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3349	likely benign
REVEL	0.273	benign-leaning
SaProt	LLR -7.68	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 12	GERP 1.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 203 kb · p 0.00059 · regional, not allelic
Overall
CADD	24.1	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 0.00204% European (non-Finnish) · 24/1,175,436 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00162% 26/1,604,724 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00204%	48,976
Remaining individualsnot grpmax-eligible	0.00161%	62,052
African / African-American	0.00134%	74,684

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.Val62Phe
Coding: c.184G>T
MANE Select: NM_020925
dbSNP: rs1270702988
Type: single nucleotide variant
Location: chr1:64470928 (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-val62phe (accessed [today's date]).

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