Is DMD p.Pro1320Arg (c.3959C>G) pathogenic?

DMD p.Pro1320Arg (c.3959C>G) is classified Conflicting classifications of pathogenicity in DMD (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.1374); Rare (popmax 0.105%, amr); Associated with Cardiovascular phenotype.

What condition is associated with DMD p.Pro1320Arg (c.3959C>G)?

DMD p.Pro1320Arg (c.3959C>G) is associated with Cardiovascular phenotype, Duchenne muscular dystrophy (ClinVar).

How common is DMD p.Pro1320Arg (c.3959C>G) in the general population?

DMD p.Pro1320Arg (c.3959C>G) is rare (popmax 0.105%, amr) (gnomAD).

What do computational predictors say about DMD p.Pro1320Arg (c.3959C>G)?

AlphaMissense predicts likely benign (score 0.1374) — an in-silico prediction, not a clinical call.

DMD p.Pro1320Arg

c.3959C>G · rs766977775 · VCV281720

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1374 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.105%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1374	likely benign
REVEL	0.106	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 2.4, phastCons 1
Regional constraint	o/e 1.36	unconstrained · MANE · 1,863 kb · p 2.4e-62 · regional, not allelic
Overall
CADD	18.26	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.105% Admixed American · 48/45,699 alleles

Filtering AF 0.0814% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.073%

Overall 0.00422% 51/1,209,518 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.105%	952
Remaining individualsnot grpmax-eligible	0.0042%	23,796
African / African-American	0.00175%	57,130

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
Protein: p.Pro1320Arg
Coding: c.3959C>G
MANE Select: NM_004006
dbSNP: rs766977775
Type: single nucleotide variant
Location: chrX:32438353 (GRCh38)

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Duchenne muscular dystrophy

Similar variants

DMD p.Pro1320= Benign/Likely benign ★★ same residue
DMD c.10086+1G>A Pathogenic ★★ same condition
DMD c.10086+1G>T Pathogenic ★★ same condition
DMD c.10086+2T>C Pathogenic ★★ same condition
DMD c.10087-2A>G Pathogenic/Likely pathogenic ★★ same condition
DMD c.10223+1G>A Pathogenic ★★ same condition
DMD c.10223+1G>C Pathogenic ★★ same condition
DMD c.10224-2A>G 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/dmd-p-pro1320arg (accessed [today's date]).

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