Is CCSAP p.Asp115Glu (c.345C>G) pathogenic?

CCSAP p.Asp115Glu (c.345C>G) is classified Uncertain significance in CCSAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-11). AlphaMissense: likely benign (0.097); Ultra-rare (popmax 0.0288%, afr).

How common is CCSAP p.Asp115Glu (c.345C>G) in the general population?

CCSAP p.Asp115Glu (c.345C>G) is ultra-rare (popmax 0.0288%, afr) (gnomAD).

What do computational predictors say about CCSAP p.Asp115Glu (c.345C>G)?

AlphaMissense predicts likely benign (score 0.097) — an in-silico prediction, not a clinical call.

CCSAP p.Asp115Glu

c.345C>G · VCV4222317

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.097 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0288%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.097	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -6.97	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 0.031	GERP 1.1
Regional constraint	o/e 0.92	unconstrained · MANE · 17 kb · p 0.13 · regional, not allelic
Overall
CADD	14.45	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 0.0288% African / African-American · 19/66,000 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0156%

Overall 0.00141% 19/1,344,560 alleles · ultra-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.Asp115Glu
Coding: c.345C>G
MANE Select: NM_145257
Type: single nucleotide variant
Location: chr1:229342121 (GRCh38)
Gene constraint: LOEUF 1.472 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.61
Residue 115: 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.Asp143Glu 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-asp115glu (accessed [today's date]).

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