Is UNC80 p.Thr2008= (c.6024C>T) pathogenic?

UNC80 p.Thr2008= (c.6024C>T) is classified Conflicting classifications of pathogenicity in UNC80 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-26). Rare (popmax 0.162%, afr); Associated with hypotonia, infantile, with psychomotor retardation and characteristic facies 2.

What condition is associated with UNC80 p.Thr2008= (c.6024C>T)?

UNC80 p.Thr2008= (c.6024C>T) is associated with hypotonia, infantile, with psychomotor retardation and characteristic facies 2 (ClinVar).

How common is UNC80 p.Thr2008= (c.6024C>T) in the general population?

UNC80 p.Thr2008= (c.6024C>T) is rare (popmax 0.162%, afr) (gnomAD).

UNC80 p.Thr2008=

Q: How is Hypotonia-speech impairment-severe cognitive delay syndrome inherited?

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

c.6024C>T · rs374791576 · VCV738631

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.162%, afr)

Conditions

hypotonia, infantile, with psychomotor retardation and characteristic facies 2

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 -8.6	GERP -4.3
Overall
CADD	4.384	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.162% African / African-American · 118/73,032 alleles

Filtering AF 0.138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.129%

Overall 0.00864% 134/1,550,980 alleles · rare exomes 70/1,398,968 · genomes 64/152,012 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.162%	619
Middle Eastern	0.0337%	2,971
Remaining individualsnot grpmax-eligible	0.0133%	7,509
Admixed American	0.00981%	10,190
European (non-Finnish)	8.72e-05%	1,146,686

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: UNC80
Protein: p.Thr2008=
Coding: c.6024C>T
MANE Select: NM_001371986
dbSNP: rs374791576
Type: single nucleotide variant
Location: chr2:209933851 (GRCh38)
Gene constraint: LOEUF 0.48 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)

Full UNC80 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hypotonia, infantile, with psychomotor retardation and characteristic facies 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hypotonia-speech impairment-severe cognitive delay syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

UNC80 c.4110+1G>C Pathogenic/Likely pathogenic ★★ same condition
UNC80 c.8772+1G>A Likely pathogenic ★★ same condition
UNC80 p.Arg1076Ter Pathogenic ★★ same condition
UNC80 p.Arg1110Ter Pathogenic ★★ same condition
UNC80 p.Arg1285Ter Pathogenic ★★ same condition
UNC80 p.Arg1355Ter Pathogenic ★★ same condition
UNC80 p.Arg137Ter Pathogenic ★★ same condition
UNC80 p.Arg174Ter 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/unc80-p-thr2008 (accessed [today's date]).

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