Is CPAMD8 p.Ala306Val (c.917C>T) pathogenic?

CPAMD8 p.Ala306Val (c.917C>T) is classified Uncertain significance in CPAMD8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-07). AlphaMissense: likely benign (0.0793); Ultra-rare (popmax 0.0787%, sas); Associated with Inborn genetic diseases.

What condition is associated with CPAMD8 p.Ala306Val (c.917C>T)?

CPAMD8 p.Ala306Val (c.917C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CPAMD8 p.Ala306Val (c.917C>T) in the general population?

CPAMD8 p.Ala306Val (c.917C>T) is ultra-rare (popmax 0.0787%, sas) (gnomAD).

What do computational predictors say about CPAMD8 p.Ala306Val (c.917C>T)?

AlphaMissense predicts likely benign (score 0.0793) — an in-silico prediction, not a clinical call.

CPAMD8 p.Ala306Val

c.917C>T · rs545086362 · VCV2409940

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0793 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0787%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0793	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -6.93	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 1.8	GERP -2.5, phastCons 0.012
Regional constraint	o/e 0.74	unconstrained · MANE · 24 kb · p 1.6e-07 · regional, not allelic
Overall
CADD	5.46	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 0.0787% South Asian · 70/88,924 alleles

Filtering AF 0.0639% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0585%

Overall 0.00821% 130/1,583,456 alleles · ultra-rare exomes 123/1,431,212 · genomes 7/152,244 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0787%	1,270
Remaining individualsnot grpmax-eligible	0.00651%	15,366
European (non-Finnish)	0.00449%	22,282
African / African-American	0.00268%	37,281
East Asian	0.00226%	44,242
Admixed American	0.00176%	56,786

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: CPAMD8
Protein: p.Ala306Val
Coding: c.917C>T
MANE Select: NM_015692
dbSNP: rs545086362
Type: single nucleotide variant
Location: chr19:16997289 (GRCh38)
Gene constraint: LOEUF 0.825 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.99

Full CPAMD8 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

CPAMD8 p.Ala306= Benign ★★ same residue
CPAMD8 c.-54C>G Uncertain significance ★★ same condition
CPAMD8 p.Ala1236Thr Uncertain significance ★★ ⚠ same condition
CPAMD8 p.Ala1468Glu Uncertain significance ★★ ⚠ same condition
CPAMD8 p.Ala490Thr Uncertain significance ★★ ⚠ same condition
CPAMD8 p.Arg1186His Uncertain significance ★★ ⚠ same condition
CPAMD8 p.Arg171Gln Uncertain significance ★★ ⚠ same condition
CPAMD8 p.Arg402His 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/cpamd8-p-ala306val (accessed [today's date]).

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