Is MED13L p.Ile1726Val (c.5176A>G) pathogenic?

MED13L p.Ile1726Val (c.5176A>G) is classified Uncertain significance in MED13L (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-28). AlphaMissense: likely benign (0.1021); Very rare (popmax 0.00446%, eas); Associated with MED13L-related disorder.

What condition is associated with MED13L p.Ile1726Val (c.5176A>G)?

MED13L p.Ile1726Val (c.5176A>G) is associated with MED13L-related disorder (ClinVar).

How common is MED13L p.Ile1726Val (c.5176A>G) in the general population?

MED13L p.Ile1726Val (c.5176A>G) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about MED13L p.Ile1726Val (c.5176A>G)?

AlphaMissense predicts likely benign (score 0.1021) — an in-silico prediction, not a clinical call.

MED13L p.Ile1726Val

c.5176A>G · rs140835810 · VCV2629362

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1021 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

MED13L-related disorder

Computational evidence

Protein change
AlphaMissense	0.1021	likely benign
REVEL	0.292	indeterminate
SaProt	LLR -6.40	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.1	GERP 1.9, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 11 kb · p 9.3e-06 · regional, not allelic
Overall
CADD	19.09	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 0.00446% East Asian · 2/44,798 alleles

Filtering AF 0.00074% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000435% 7/1,609,334 alleles · very rare exomes 6/1,458,068 · genomes 1/151,266 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,399
African / African-American	0.00268%	37,277
European (non-Finnish)	0.000254%	393,241

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.Ile1726Val
Coding: c.5176A>G
MANE Select: NM_015335
dbSNP: rs140835810
Type: single nucleotide variant
Location: chr12:115980938 (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

MED13L-related disorder

Similar variants

MED13L p.Arg1760Ter Pathogenic ★★ same condition
MED13L p.Arg1900Ter Pathogenic ★★ same condition
MED13L p.Gln2123Ter Pathogenic/Likely pathogenic ★★ same condition
MED13L p.Gln2186Ter Likely pathogenic ★★ same condition
MED13L p.Gln2119Ter Pathogenic ★ same condition
MED13L p.Gln223Ter Likely pathogenic ★ same condition
MED13L p.Gln506Ter Pathogenic ★ same condition
MED13L p.Glu1348Ter Likely pathogenic ★ 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-ile1726val (accessed [today's date]).

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