Is UNC80 p.Ser166Cys (c.497C>G) pathogenic?

UNC80 p.Ser166Cys (c.497C>G) is classified Uncertain significance in UNC80 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-17). AlphaMissense: likely benign (0.0678); Absent from gnomAD v4.1.

How common is UNC80 p.Ser166Cys (c.497C>G) in the general population?

UNC80 p.Ser166Cys (c.497C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about UNC80 p.Ser166Cys (c.497C>G)?

AlphaMissense predicts likely benign (score 0.0678) — an in-silico prediction, not a clinical call.

UNC80 p.Ser166Cys

c.497C>G · rs2470895701 · VCV2803149

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0678 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0678	likely benign
REVEL	0.065	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 4.9	GERP 1.7, phastCons 0.98
Regional constraint	o/e 0.91	unconstrained · MANE · 57 kb · p 0.0051 · regional, not allelic
Overall
CADD	24.7	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: UNC80
Protein: p.Ser166Cys
Coding: c.497C>G
MANE Select: NM_001371986
dbSNP: rs2470895701
Type: single nucleotide variant
Location: chr2:209777456 (GRCh38)
Gene constraint: LOEUF 0.48 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 166: the 'disordered' region

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

Similar variants

UNC80 p.Ser166Pro Uncertain significance ★★ ⚠ 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
UNC80 p.Arg1179Ter Pathogenic/Likely 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-ser166cys (accessed [today's date]).

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