Is UNC80 p.Ala3192Val (c.9575C>T) pathogenic?

UNC80 p.Ala3192Val (c.9575C>T) is classified Uncertain significance in UNC80 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-13). AlphaMissense: likely benign (0.0681); Very rare (popmax 0.00595%, sas).

How common is UNC80 p.Ala3192Val (c.9575C>T) in the general population?

UNC80 p.Ala3192Val (c.9575C>T) is very rare (popmax 0.00595%, sas) (gnomAD).

What do computational predictors say about UNC80 p.Ala3192Val (c.9575C>T)?

AlphaMissense predicts likely benign (score 0.0681) — an in-silico prediction, not a clinical call.

UNC80 p.Ala3192Val

c.9575C>T · rs1224904650 · VCV1913384

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0681 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00595%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0681	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.9	GERP -0.63
Regional constraint	o/e 0.93	unconstrained · MANE · 3,374 bp · p 0.24 · regional, not allelic
Overall
CADD	10.49	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 is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A3126V vs ClinVar A3192V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00595% South Asian · 5/84,054 alleles

Filtering AF 0.00234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00146%

Overall 0.00135% 21/1,551,682 alleles · very rare exomes 19/1,399,530 · genomes 2/152,152 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00595%	16,811
Admixed American	0.00196%	50,994
European (non-Finnish)	0.00131%	76,466

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.Ala3192Val
Coding: c.9575C>T
MANE Select: NM_001371986
dbSNP: rs1224904650
Type: single nucleotide variant
Location: chr2:209994131 (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

Similar variants

UNC80 p.Ala3192Thr Likely benign ★★ same residue
UNC80 p.Ala3192= Likely benign ★ same residue
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
UNC80 p.Arg1076Ter Pathogenic ★★ same type
UNC80 p.Arg1110Ter 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-ala3192val (accessed [today's date]).

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