Is MCM3AP p.Ala884Val (c.2651C>T) pathogenic?

MCM3AP p.Ala884Val (c.2651C>T) is classified Uncertain significance in MCM3AP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-06). AlphaMissense: likely benign (0.2421); Ultra-rare (popmax 0.0133%, amr); Associated with Inborn genetic diseases.

What condition is associated with MCM3AP p.Ala884Val (c.2651C>T)?

MCM3AP p.Ala884Val (c.2651C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MCM3AP p.Ala884Val (c.2651C>T) in the general population?

MCM3AP p.Ala884Val (c.2651C>T) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

What do computational predictors say about MCM3AP p.Ala884Val (c.2651C>T)?

AlphaMissense predicts likely benign (score 0.2421) — an in-silico prediction, not a clinical call.

MCM3AP p.Ala884Val

c.2651C>T · rs758882933 · VCV1424391

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2421 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2421	likely benign
REVEL	0.219	benign-leaning
SaProt	LLR -7.96	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 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 6,524 bp · p 0.0001 · regional, not allelic
Overall
CADD	24.6	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 0.0133% Admixed American · 8/59,970 alleles

Filtering AF 0.00662% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00483%

Overall 0.00149% 24/1,613,660 alleles · ultra-rare exomes 22/1,461,458 · genomes 2/152,202 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,496
East Asian	0.0111%	8,975
South Asian	0.0011%	90,982
European (non-Finnish)	0.000848%	117,989

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: MCM3AP
Protein: p.Ala884Val
Coding: c.2651C>T
MANE Select: NM_003906
dbSNP: rs758882933
Type: single nucleotide variant
Location: chr21:46267120 (GRCh38)
Gene constraint: LOEUF 0.769 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.83 · 7 PDB
Residue 884: the pci domain; the 'interaction with pcid2 and sem1' region; an α-helix

Full MCM3AP 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

MCM3AP p.Ala884= Likely benign ★ same residue
MCM3AP p.Ala1102Ser Uncertain significance ★★ ⚠ same condition
MCM3AP p.Ala1117Val Uncertain significance ★★ ⚠ same condition
MCM3AP p.Ala1283Thr Uncertain significance ★★ ⚠ same condition
MCM3AP p.Ala172Ser Uncertain significance ★★ ⚠ same condition
MCM3AP p.Ala17Gly Uncertain significance ★★ ⚠ same condition
MCM3AP p.Ala277Pro Uncertain significance ★★ ⚠ same condition
MCM3AP p.Ala499Thr 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/mcm3ap-p-ala884val (accessed [today's date]).

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