Is CCSAP p.Asp50Glu (c.150C>A) pathogenic?

CCSAP p.Asp50Glu (c.150C>A) is classified Uncertain significance in CCSAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-01). AlphaMissense: ambiguous (0.4057); Very rare (popmax 0.000448%, nfe).

How common is CCSAP p.Asp50Glu (c.150C>A) in the general population?

CCSAP p.Asp50Glu (c.150C>A) is very rare (popmax 0.000448%, nfe) (gnomAD).

What do computational predictors say about CCSAP p.Asp50Glu (c.150C>A)?

AlphaMissense predicts ambiguous (score 0.4057) — an in-silico prediction, not a clinical call.

CCSAP p.Asp50Glu

c.150C>A · VCV3997818

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4057 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000448%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4057	ambiguous
REVEL	0.011	strongly benign-leaning
SaProt	LLR -4.85	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP -1.1, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 17 kb · p 0.13 · regional, not allelic
Overall
CADD	18.78	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 0.000448% European (non-Finnish) · 5/1,115,342 alleles

Filtering AF 0.000131% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.5e-05%

Overall 0.000339% 5/1,476,794 alleles · very rare

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: CCSAP
Protein: p.Asp50Glu
Coding: c.150C>A
MANE Select: NM_145257
Type: single nucleotide variant
Location: chr1:229342316 (GRCh38)
Gene constraint: LOEUF 1.472 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.61
Residue 50: the 'disordered' region

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

Similar variants

CCSAP p.Ala113Thr Uncertain significance ★ ⚠ same type
CCSAP p.Ala208Thr Uncertain significance ★ ⚠ same type
CCSAP p.Arg14His Uncertain significance ★ ⚠ same type
CCSAP p.Arg152Gln Uncertain significance ★ ⚠ same type
CCSAP p.Arg224Gly Uncertain significance ★ ⚠ same type
CCSAP p.Arg235Ser Uncertain significance ★ ⚠ same type
CCSAP p.Arg37Cys Uncertain significance ★ ⚠ same type
CCSAP p.Asp115Glu Uncertain significance ★ ⚠ same type

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/ccsap-p-asp50glu (accessed [today's date]).

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