Is MED13L p.Met1326Val (c.3976A>G) pathogenic?

MED13L p.Met1326Val (c.3976A>G) is classified Uncertain significance in MED13L (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-06). AlphaMissense: likely benign (0.2136); Very rare (popmax 0.00178%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MED13L p.Met1326Val (c.3976A>G)?

MED13L p.Met1326Val (c.3976A>G) is associated with Inborn genetic diseases (ClinVar).

How common is MED13L p.Met1326Val (c.3976A>G) in the general population?

MED13L p.Met1326Val (c.3976A>G) is very rare (popmax 0.00178%, nfe) (gnomAD).

What do computational predictors say about MED13L p.Met1326Val (c.3976A>G)?

AlphaMissense predicts likely benign (score 0.2136) — an in-silico prediction, not a clinical call.

MED13L p.Met1326Val

c.3976A>G · VCV4106077

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2136 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2136	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -3.86	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.2	GERP 2.3, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 4,192 bp · p 0.061 · regional, not allelic
Overall
CADD	19.77	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 0.00178% European (non-Finnish) · 21/1,180,000 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00136% 22/1,613,768 alleles · very rare exomes 22/1,461,488 · genomes 0/152,280 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00178%	56,191
Remaining individualsnot grpmax-eligible	0.0016%	62,466

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: MED13L
Protein: p.Met1326Val
Coding: c.3976A>G
MANE Select: NM_015335
Type: single nucleotide variant
Location: chr12:115987247 (GRCh38)
Gene constraint: LOEUF 0.041 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 56.79

Full MED13L 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

MED13L p.Arg564Ter Pathogenic ★★ same condition
MED13L p.Gln2140Ter Pathogenic ★★ same condition
MED13L p.Pro869Ser Likely pathogenic ★★ ⚠ same condition
MED13L c.2997-2A>G Uncertain significance ★★ same condition
MED13L c.820+4A>G Uncertain significance ★★ same condition
MED13L p.Ala1623Ser Uncertain significance ★★ ⚠ same condition
MED13L p.Ala345Asp Uncertain significance ★★ ⚠ same condition
MED13L p.Arg973Gln 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/med13l-p-met1326val (accessed [today's date]).

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