Is MLEC p.Ala13Val (c.38C>T) pathogenic?

MLEC p.Ala13Val (c.38C>T) is classified Uncertain significance in MLEC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely benign (0.1738); Ultra-rare (popmax 0.0407%, sas).

How common is MLEC p.Ala13Val (c.38C>T) in the general population?

MLEC p.Ala13Val (c.38C>T) is ultra-rare (popmax 0.0407%, sas) (gnomAD).

What do computational predictors say about MLEC p.Ala13Val (c.38C>T)?

AlphaMissense predicts likely benign (score 0.1738) — an in-silico prediction, not a clinical call.

MLEC p.Ala13Val

c.38C>T · VCV4829378

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1738 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0407%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1738	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -6.62	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 0.44	GERP 0.31, phastCons 0.98
Regional constraint	o/e 0.61	unconstrained · MANE · 9,245 bp · p 6.6e-15 · regional, not allelic
Overall
CADD	21.9	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 0.0407% South Asian · 24/58,990 alleles

Filtering AF 0.028% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0238%

Overall 0.00172% 24/1,395,248 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: MLEC
Protein: p.Ala13Val
Coding: c.38C>T
MANE Select: NM_014730
Type: single nucleotide variant
Location: chr12:120687334 (GRCh38)
Gene constraint: LOEUF 0.5 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 81.03 · 5 PDB

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

Similar variants

MLEC c.414+28C>T Benign ★★ same type
MLEC p.Ala25Thr Uncertain significance ★ ⚠ same type
MLEC p.Ala25Val Uncertain significance ★ ⚠ same type
MLEC p.Ala39Val Uncertain significance ★ ⚠ same type
MLEC p.Arg259Cys Uncertain significance ★ ⚠ same type
MLEC p.Asp217Gly Uncertain significance ★ same type
MLEC p.Glu107Gly Uncertain significance ★ same type
MLEC p.Glu236Lys 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/mlec-p-ala13val (accessed [today's date]).

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