Is CPAMD8 p.Arg950Ser (c.2850A>C) pathogenic?

CPAMD8 p.Arg950Ser (c.2850A>C) is classified Uncertain significance in CPAMD8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-27). AlphaMissense: ambiguous (0.4103); Very rare (popmax 0.0042%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CPAMD8 p.Arg950Ser (c.2850A>C)?

CPAMD8 p.Arg950Ser (c.2850A>C) is associated with Inborn genetic diseases (ClinVar).

How common is CPAMD8 p.Arg950Ser (c.2850A>C) in the general population?

CPAMD8 p.Arg950Ser (c.2850A>C) is very rare (popmax 0.0042%, nfe) (gnomAD).

What do computational predictors say about CPAMD8 p.Arg950Ser (c.2850A>C)?

AlphaMissense predicts ambiguous (score 0.4103) — an in-silico prediction, not a clinical call.

CPAMD8 p.Arg950Ser

c.2850A>C · rs755022510 · VCV2589310

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4103 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0042%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4103	ambiguous
REVEL	0.153	moderately benign-leaning
SaProt	LLR -5.62	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -0.81, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 83 kb · p 0.29 · regional, not allelic
Overall
CADD	18.31	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 0.0042% European (non-Finnish) · 49/1,168,036 alleles

Filtering AF 0.00321% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00289%

Overall 0.00313% 50/1,597,480 alleles · very rare exomes 46/1,445,288 · genomes 4/152,192 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0042%	23,837
Remaining individualsnot grpmax-eligible	0.00162%	61,678

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.Arg950Ser
Coding: c.2850A>C
MANE Select: NM_015692
dbSNP: rs755022510
Type: single nucleotide variant
Location: chr19:16929236 (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.Arg950Thr Uncertain significance ★ ⚠ 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-arg950ser (accessed [today's date]).

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