Is UNC80 p.Pro341Ser (c.1021C>T) pathogenic?

UNC80 p.Pro341Ser (c.1021C>T) is classified Likely benign in UNC80 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-02-27). AlphaMissense: ambiguous (0.472); Rare (popmax 0.167%, nfe); Associated with Inborn genetic diseases.

What condition is associated with UNC80 p.Pro341Ser (c.1021C>T)?

UNC80 p.Pro341Ser (c.1021C>T) is associated with Inborn genetic diseases (ClinVar).

How common is UNC80 p.Pro341Ser (c.1021C>T) in the general population?

UNC80 p.Pro341Ser (c.1021C>T) is rare (popmax 0.167%, nfe) (gnomAD).

What do computational predictors say about UNC80 p.Pro341Ser (c.1021C>T)?

AlphaMissense predicts ambiguous (score 0.472) — an in-silico prediction, not a clinical call.

UNC80 p.Pro341Ser

c.1021C>T · rs199667714 · VCV3049153

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.472 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.167%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.472	ambiguous
REVEL	0.127	moderately benign-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 57 kb · p 0.0051 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.167% European (non-Finnish) · 1,917/1,147,006 alleles

Filtering AF 0.161% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.158%

Overall 0.135% 2,088/1,551,776 alleles · rare exomes 1,958/1,399,496 · genomes 130/152,280 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.167%	598
Remaining individualsnot grpmax-eligible	0.161%	620
Finnishnot grpmax-eligible	0.0884%	1,131
African / African-American	0.0219%	4,572
Admixed American	0.0098%	10,200

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.Pro341Ser
Coding: c.1021C>T
MANE Select: NM_001371986
dbSNP: rs199667714
Type: single nucleotide variant
Location: chr2:209813662 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

UNC80 p.Pro341Leu Uncertain significance ★ same residue
UNC80 p.Ala1338Ser Uncertain significance ★★ same condition
UNC80 p.Ala1886Thr Uncertain significance ★★ ⚠ same condition
UNC80 p.Ala1907Thr Uncertain significance ★★ ⚠ same condition
UNC80 p.Ala2284Val Uncertain significance ★★ same condition
UNC80 p.Ala537Thr Uncertain significance ★★ ⚠ same condition
UNC80 p.Ala676Gly Uncertain significance ★★ same condition
UNC80 p.Ala864Gly Uncertain significance ★★ ⚠ 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-pro341ser (accessed [today's date]).

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