Is DAG1 p.Pro62Leu (c.185C>T) pathogenic?

DAG1 p.Pro62Leu (c.185C>T) is classified Uncertain significance in DAG1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.1278); Ultra-rare (popmax 0.0825%, mid); Associated with Inborn genetic diseases.

How common is DAG1 p.Pro62Leu (c.185C>T) in the general population?

DAG1 p.Pro62Leu (c.185C>T) is ultra-rare (popmax 0.0825%, mid) (gnomAD).

What do computational predictors say about DAG1 p.Pro62Leu (c.185C>T)?

AlphaMissense predicts likely benign (score 0.1278) — an in-silico prediction, not a clinical call.

DAG1 p.Pro62Leu

Q: What condition is associated with DAG1 p.Pro62Leu (c.185C>T)?

DAG1 p.Pro62Leu (c.185C>T) is associated with Inborn genetic diseases, autosomal recessive limb-girdle muscular dystrophy type 2P, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9 (ClinVar).

c.185C>T · rs375938350 · VCV282776

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.1278 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0825%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1278	likely benign
REVEL	0.48	indeterminate
SaProt	LLR -8.89	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 21 kb · p 0.0053 · regional, not allelic
Overall
CADD	21.8	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 0.0825% Middle Eastern · 5/6,062 alleles

Filtering AF 0.0324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.021%

Overall 0.00923% 149/1,614,184 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0825%	1,212
Remaining individualsnot grpmax-eligible	0.0208%	4,808
South Asian	0.0154%	6,506
European (non-Finnish)	0.00975%	10,261
Finnishnot grpmax-eligible	0.00312%	32,016

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: DAG1
Protein: p.Pro62Leu
Coding: c.185C>T
MANE Select: NM_004393
dbSNP: rs375938350
Type: single nucleotide variant
Location: chr3:49510719 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.44 · 8 PDB
Residue 62: the 'required for laminin recognition' region

Full DAG1 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

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2P muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9

Similar variants

DAG1 p.Ser14Ter Pathogenic ★★ same condition
DAG1 p.Trp110Ter Pathogenic/Likely pathogenic ★★ same condition
DAG1 p.Ala135Ser Uncertain significance ★★ ⚠ same condition
DAG1 p.Ala135Thr Uncertain significance ★★ ⚠ same condition
DAG1 p.Ala279Ser Uncertain significance ★★ ⚠ same condition
DAG1 p.Ala285Thr Uncertain significance ★★ ⚠ same condition
DAG1 p.Ala285Val Uncertain significance ★★ ⚠ same condition
DAG1 p.Ala610Val 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/dag1-p-pro62leu (accessed [today's date]).

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