Is UNC80 p.Ala3170= (c.9510G>A) pathogenic?

UNC80 p.Ala3170= (c.9510G>A) is classified Conflicting classifications of pathogenicity in UNC80 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-07-10). Very rare (popmax 0.00735%, eas); Associated with intellectual disability.

What condition is associated with UNC80 p.Ala3170= (c.9510G>A)?

UNC80 p.Ala3170= (c.9510G>A) is associated with intellectual disability (ClinVar).

How common is UNC80 p.Ala3170= (c.9510G>A) in the general population?

UNC80 p.Ala3170= (c.9510G>A) is very rare (popmax 0.00735%, eas) (gnomAD).

UNC80 p.Ala3170=

c.9510G>A · rs756716727 · VCV1408814

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00735%, eas)

Conditions

intellectual disability

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.91	acceptor gain · deltas
Pangolin	Δ0.63	gain · loss 0.05 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -6.6	GERP -4.3
Overall
CADD	12.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00735% East Asian · 3/40,834 alleles

Filtering AF 0.00422% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00383%

Overall 0.00452% 70/1,548,684 alleles · very rare exomes 63/1,396,714 · genomes 7/151,970 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00735%	13,611
European (non-Finnish)	0.00532%	18,780
South Asian	0.00358%	27,923
Admixed American	0.00198%	50,512
Remaining individualsnot grpmax-eligible	0.00167%	60,012
African / African-American	0.00137%	72,868

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.Ala3170=
Coding: c.9510G>A
MANE Select: NM_001371986
dbSNP: rs756716727
Type: single nucleotide variant
Location: chr2:209994066 (GRCh38)
Gene constraint: LOEUF 0.48 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3170: the 'disordered' region

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

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

UNC80 p.Ala3170Val Conflicting classifications of pathogenicity ★ ⚠ same residue
UNC80 p.Arg137Ter Pathogenic ★★ same condition
UNC80 p.Ala1788Gly Uncertain significance ★ same condition
UNC80 p.Gln602His Conflicting classifications of pathogenicity ★ ⚠ same condition
UNC80 c.4110+1G>C Pathogenic/Likely pathogenic ★★ same type
UNC80 c.7287-1G>A Likely pathogenic ★★ same type
UNC80 c.8772+1G>A Likely pathogenic ★★ same type
UNC80 p.Arg1069Ter Pathogenic ★★ 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/unc80-p-ala3170 (accessed [today's date]).

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