Is CDH15 p.Val54Ile (c.160G>A) pathogenic?

CDH15 p.Val54Ile (c.160G>A) is classified Conflicting classifications of pathogenicity in CDH15 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-01-01). AlphaMissense: likely benign (0.0987); Rare (popmax 0.445%, sas); Associated with intellectual disability.

What condition is associated with CDH15 p.Val54Ile (c.160G>A)?

CDH15 p.Val54Ile (c.160G>A) is associated with intellectual disability (ClinVar).

How common is CDH15 p.Val54Ile (c.160G>A) in the general population?

CDH15 p.Val54Ile (c.160G>A) is rare (popmax 0.445%, sas) (gnomAD).

What do computational predictors say about CDH15 p.Val54Ile (c.160G>A)?

AlphaMissense predicts likely benign (score 0.0987) — an in-silico prediction, not a clinical call.

CDH15 p.Val54Ile

c.160G>A · rs138572161 · VCV739776

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0987 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.445%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.0987	likely benign
REVEL	0.199	benign-leaning
SaProt	LLR -6.92	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 11	GERP 1.2, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 23 kb · p 5e-10 · regional, not allelic
Overall
CADD	22.4	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 0.445% South Asian · 405/90,932 alleles

Filtering AF 0.41% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.396%

Overall 0.0382% 616/1,610,922 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.445%	225
African / African-American	0.149%	669
Remaining individualsnot grpmax-eligible	0.0561%	1,781
Middle Eastern	0.0331%	3,021
Admixed American	0.0101%	9,946
European (non-Finnish)	0.00467%	21,425
Finnishnot grpmax-eligible	0.00158%	63,396

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: CDH15
Protein: p.Val54Ile
Coding: c.160G>A
MANE Select: NM_004933
dbSNP: rs138572161
Type: single nucleotide variant
Location: chr16:89179533 (GRCh38)
Gene constraint: LOEUF 1.41 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.70

Full CDH15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDH15 p.Val54Leu Uncertain significance ★ ⚠ same residue
CDH3 p.Val54= Likely benign ★ same residue
CDH15 p.Ala246Val Conflicting classifications of pathogenicity ★ ⚠ same condition
CDH15 p.Ala597Val Uncertain significance ★ ⚠ same condition
CDH15 p.Arg44Trp Conflicting classifications of pathogenicity ★ ⚠ same condition
CDH15 p.Glu337Lys Conflicting classifications of pathogenicity ★ ⚠ same condition
CDH15 p.Thr404Ile Conflicting classifications of pathogenicity ★ ⚠ same condition
CDH15 p.Tyr763Cys Likely benign ★ ⚠ 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/cdh15-p-val54ile (accessed [today's date]).

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