Is DMTN p.Ile187= (c.561C>T) pathogenic?

DMTN p.Ile187= (c.561C>T) is classified Likely benign in DMTN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-12). Rare (popmax 0.112%, afr).

How common is DMTN p.Ile187= (c.561C>T) in the general population?

DMTN p.Ile187= (c.561C>T) is rare (popmax 0.112%, afr) (gnomAD).

DMTN p.Ile187=

c.561C>T · VCV3502762

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.112%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.9	GERP -3.8
Overall
CADD	3.862	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.112% African / African-American · 84/74,884 alleles

Filtering AF 0.0928% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0856%

Overall 0.00694% 112/1,613,534 alleles · rare exomes 53/1,461,358 · genomes 59/152,176 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.112%	891
Middle Eastern	0.0165%	6,078
Remaining individualsnot grpmax-eligible	0.00801%	12,491
Admixed American	0.00501%	19,978
European (non-Finnish)	0.00161%	62,094

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: DMTN
Protein: p.Ile187=
Coding: c.561C>T
MANE Select: NM_001387751
Type: single nucleotide variant
Location: chr8:22070291 (GRCh38)
Gene constraint: LOEUF 0.695 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.03 · 2 PDB
Residue 187: the 'disordered' region

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

Similar variants

DMTN c.295-2A>T Uncertain significance ★ same type
DMTN c.604+2T>G Uncertain significance ★ same type
DMTN p.Ala199Gly Uncertain significance ★ ⚠ same type
DMTN p.Arg135Cys Uncertain significance ★ ⚠ same type
DMTN p.Arg150Lys Uncertain significance ★ ⚠ same type
DMTN p.Arg208Trp Uncertain significance ★ ⚠ same type
DMTN p.Arg212Trp Uncertain significance ★ ⚠ same type
DMTN p.Arg236Leu Uncertain significance ★ ⚠ 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/dmtn-p-ile187 (accessed [today's date]).

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