Is DSG4 p.Met1007Thr (c.3020T>C) pathogenic?

DSG4 p.Met1007Thr (c.3020T>C) is classified Conflicting classifications of pathogenicity in DSG4 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-05). AlphaMissense: likely benign (0.1005); Low-frequency (popmax 1.78%, mid); Associated with hypotrichosis 6.

What condition is associated with DSG4 p.Met1007Thr (c.3020T>C)?

DSG4 p.Met1007Thr (c.3020T>C) is associated with hypotrichosis 6 (ClinVar).

How common is DSG4 p.Met1007Thr (c.3020T>C) in the general population?

DSG4 p.Met1007Thr (c.3020T>C) is low-frequency (popmax 1.78%, mid) (gnomAD).

How is Hypotrichosis simplex inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DSG4 p.Met1007Thr (c.3020T>C)?

AlphaMissense predicts likely benign (score 0.1005) — an in-silico prediction, not a clinical call.

DSG4 p.Met1007Thr

c.3020T>C · rs145343712 · VCV326456

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1005 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.78%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hypotrichosis 6

Computational evidence

Protein change
AlphaMissense	0.1005	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -5.38	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.1	GERP -3.6, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 37 kb · p 0.015 · regional, not allelic
Overall
CADD	14.98	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 1.78% Middle Eastern · 108/6,056 alleles

Filtering AF 1.51% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.41%

Overall 0.0843% 1,359/1,612,776 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.78%	56
South Asian	0.18%	555
Admixed American	0.177%	566
Ashkenazi Jewishnot grpmax-eligible	0.128%	778
Remaining individualsnot grpmax-eligible	0.127%	790
European (non-Finnish)	0.0713%	1,403
African / African-American	0.024%	4,168
Finnishnot grpmax-eligible	0.00937%	10,667

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: DSG4
Protein: p.Met1007Thr
Coding: c.3020T>C
dbSNP: rs145343712
Type: single nucleotide variant
Location: chr18:31413492 (GRCh38)

Full DSG4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hypotrichosis 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hypotrichosis simplex (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Childhood

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/dsg4-p-met1007thr (accessed [today's date]).

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