Is MED13L p.Thr1663= (c.4989G>A) pathogenic?

MED13L p.Thr1663= (c.4989G>A) is classified Likely benign in MED13L (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-31). Ultra-rare (popmax 0.0121%, sas); Associated with dextro-looped transposition of the great arteries.

What condition is associated with MED13L p.Thr1663= (c.4989G>A)?

MED13L p.Thr1663= (c.4989G>A) is associated with dextro-looped transposition of the great arteries (ClinVar).

How common is MED13L p.Thr1663= (c.4989G>A) in the general population?

MED13L p.Thr1663= (c.4989G>A) is ultra-rare (popmax 0.0121%, sas) (gnomAD).

MED13L p.Thr1663=

c.4989G>A · rs755349611 · VCV695333

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, sas)

Conditions

dextro-looped transposition of the great arteries

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.01	strongly benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -9.9	GERP -3.8
Overall
CADD	1.329	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0121% South Asian · 11/91,090 alleles

Filtering AF 0.00676% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00522%

Overall 0.00595% 96/1,613,918 alleles · ultra-rare exomes 78/1,461,798 · genomes 18/152,120 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.132%	759
South Asiangrpmax	0.0121%	8,281
Admixed American	0.00667%	14,999
Remaining individualsnot grpmax-eligible	0.0064%	15,620
European (non-Finnish)	0.00305%	32,777
East Asian	0.00223%	44,874
Finnishnot grpmax-eligible	0.00156%	64,010

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Thr1663=
Coding: c.4989G>A
MANE Select: NM_015335
dbSNP: rs755349611
Type: single nucleotide variant
Location: chr12:115982570 (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

dextro-looped transposition of the great arteries — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MED13L p.Thr1663Met Conflicting classifications of pathogenicity ★ ⚠ same residue
MED13L p.Arg379Ter Pathogenic ★★ same condition
MED13L p.Asp860Gly Pathogenic/Likely pathogenic ★★ ⚠ same condition
MED13L p.Gln691Ter Pathogenic ★★ same condition
MED13L p.Pro2094Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
MED13L p.Ser2163Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
MED13L p.Thr2162Met Pathogenic/Likely pathogenic ★★ ⚠ same condition
MED13L p.Trp88Ter 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-thr1663 (accessed [today's date]).

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