Is DMD c.649+145T>C pathogenic?

DMD c.649+145T>C is classified Benign in DMD (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-14). Common (popmax 55.8%, amr) — too common for a highly-penetrant pathogenic allele.

DMD c.649+145T>C

Q: How common is DMD c.649+145T>C in the general population?

DMD c.649+145T>C is common (popmax 55.8%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs1015509 · VCV671236

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 55.8%, amr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +145	deep intronic (+145 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP -0.61, phastCons 1
Non-coding constraint	—	not assessed · autosomes only, so chrX has no window · absence ≠ unconstrained
Overall
CADD	3.559	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 55.8% Admixed American · 20,135/36,109 alleles

Filtering AF 55.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 54.9%

Overall 48.9% 247,020/505,532 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	75.2%	1
Finnishnot grpmax-eligible	56%	2
Admixed Americangrpmax	55.8%	2
European (non-Finnish)	54.2%	2
Ashkenazi Jewishnot grpmax-eligible	49.8%	2
Remaining individualsnot grpmax-eligible	48.8%	2
Middle Eastern	37.9%	3
East Asian	30.4%	3
African / African-American	29.7%	3
South Asian	29%	3

Amish 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: DMD
Coding: c.649+145T>C
MANE Select: NM_004006
dbSNP: rs1015509
Type: single nucleotide variant
Location: chrX:32809348 (GRCh38)

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

Similar variants

DMD c.10086+1G>A Pathogenic ★★ same type
DMD c.10086+1G>T Pathogenic ★★ same type
DMD c.10086+2T>C Pathogenic ★★ same type
DMD c.10087-2A>G Pathogenic/Likely pathogenic ★★ same type
DMD c.10223+1G>A Pathogenic ★★ same type
DMD c.10223+1G>C Pathogenic ★★ same type
DMD c.10224-2A>G Likely pathogenic ★★ same type
DMD c.10554-2A>G Pathogenic/Likely pathogenic ★★ 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/dmd-c-649-plus-145t-c (accessed [today's date]).

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