Is MCTP2 p.Ser7Pro (c.19T>C) pathogenic?

MCTP2 p.Ser7Pro (c.19T>C) is classified Uncertain significance in MCTP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-06). AlphaMissense: likely benign (0.2452); Ultra-rare (popmax 0.0462%, sas); Associated with Inborn genetic diseases.

What condition is associated with MCTP2 p.Ser7Pro (c.19T>C)?

MCTP2 p.Ser7Pro (c.19T>C) is associated with Inborn genetic diseases (ClinVar).

How common is MCTP2 p.Ser7Pro (c.19T>C) in the general population?

MCTP2 p.Ser7Pro (c.19T>C) is ultra-rare (popmax 0.0462%, sas) (gnomAD).

What do computational predictors say about MCTP2 p.Ser7Pro (c.19T>C)?

AlphaMissense predicts likely benign (score 0.2452) — an in-silico prediction, not a clinical call.

MCTP2 p.Ser7Pro

c.19T>C · rs761478276 · VCV2287856

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2452 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0462%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2452	likely benign
REVEL	0.335	indeterminate
SaProt	LLR -8.11	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 2.1, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 181 kb · p 0.00043 · regional, not allelic
Overall
CADD	23.2	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 0.0462% South Asian · 42/90,926 alleles

Filtering AF 0.0351% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0312%

Overall 0.00292% 47/1,612,230 alleles · ultra-rare exomes 45/1,460,118 · genomes 2/152,112 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0462%	2,165
Remaining individualsnot grpmax-eligible	0.00641%	15,601
African / African-American	0.00134%	74,832

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: MCTP2
Protein: p.Ser7Pro
Coding: c.19T>C
MANE Select: NM_001385001
dbSNP: rs761478276
Type: single nucleotide variant
Location: chr15:94298284 (GRCh38)
Gene constraint: LOEUF 1.328 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.73 · 1 PDB

Full MCTP2 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

MCTP2 p.Ala615Thr Uncertain significance ★★ ⚠ same condition
MCTP2 p.Thr227Met Uncertain significance ★★ ⚠ same condition
MCTP2 p.Leu864Pro Likely benign ★★ same condition
MCTP2 p.Ala110Gly Uncertain significance ★ ⚠ same condition
MCTP2 p.Ala123Asp Uncertain significance ★ ⚠ same condition
MCTP2 p.Ala125Thr Uncertain significance ★ ⚠ same condition
MCTP2 p.Ala333Thr Uncertain significance ★ ⚠ same condition
MCTP2 p.Ala484Val 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/mctp2-p-ser7pro (accessed [today's date]).

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