Is MCTP2 p.Leu796Val (c.2386C>G) pathogenic?

MCTP2 p.Leu796Val (c.2386C>G) is classified Benign in MCTP2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.1998); Low-frequency (popmax 3.71%, nfe).

How common is MCTP2 p.Leu796Val (c.2386C>G) in the general population?

MCTP2 p.Leu796Val (c.2386C>G) is low-frequency (popmax 3.71%, nfe) (gnomAD).

What do computational predictors say about MCTP2 p.Leu796Val (c.2386C>G)?

AlphaMissense predicts likely benign (score 0.1998) — an in-silico prediction, not a clinical call.

MCTP2 p.Leu796Val

c.2386C>G · rs1596842542 · VCV726459

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1998 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.71%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1998	likely benign
REVEL	0.403	indeterminate
SaProt	LLR -10.98	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.27	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 5.9	GERP 1.6, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 181 kb · p 0.00043 · regional, not allelic
Overall
CADD	24.0	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 3.71% European (non-Finnish) · 30,277/815,834 alleles

Filtering AF 3.68% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.66%

Overall 2.74% 33,218/1,214,234 alleles · low-frequency exomes 33,218/1,062,502 · genomes 0/151,732 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	3.71%	27
Remaining individualsnot grpmax-eligible	2.15%	47
Middle Eastern	1.49%	67
African / African-American	1.08%	92
Ashkenazi Jewishnot grpmax-eligible	0.807%	124
South Asian	0.798%	125
East Asian	0.342%	292
Admixed American	0.0556%	1,798
Finnishnot grpmax-eligible	0.0252%	3,972

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.Leu796Val
Coding: c.2386C>G
MANE Select: NM_001385001
dbSNP: rs1596842542
Type: single nucleotide variant
Location: chr15:94470358 (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

Similar variants

MCTP2 p.Ala615Thr Uncertain significance ★★ ⚠ same type
MCTP2 p.Thr227Met Uncertain significance ★★ ⚠ same type
MCTP2 c.1583-6T>C Benign ★★ same type
MCTP2 c.970-10A>G Likely benign ★★ same type
MCTP2 p.Ala60Thr Benign ★★ same type
MCTP2 p.Ala695Thr Benign ★★ same type
MCTP2 p.Ala877Thr Benign ★★ same type
MCTP2 p.Arg340His Benign ★★ 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/mctp2-p-leu796val (accessed [today's date]).

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