Is UNC80 p.Ser301Phe (c.902C>T) pathogenic?

UNC80 p.Ser301Phe (c.902C>T) is classified Conflicting classifications of pathogenicity in UNC80 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-09-28). AlphaMissense: likely benign (0.1504); Rare (popmax 0.213%, sas).

How common is UNC80 p.Ser301Phe (c.902C>T) in the general population?

UNC80 p.Ser301Phe (c.902C>T) is rare (popmax 0.213%, sas) (gnomAD).

What do computational predictors say about UNC80 p.Ser301Phe (c.902C>T)?

AlphaMissense predicts likely benign (score 0.1504) — an in-silico prediction, not a clinical call.

UNC80 p.Ser301Phe

c.902C>T · rs564175384 · VCV1427336

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1504 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.213%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1504	likely benign
REVEL	0.201	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 57 kb · p 0.0051 · regional, not allelic
Overall
CADD	26.5	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 0.213% South Asian · 194/91,076 alleles

Filtering AF 0.188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.179%

Overall 0.0137% 221/1,614,140 alleles · rare exomes 215/1,461,800 · genomes 6/152,340 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.213%	469
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0048%	20,836
East Asian	0.00223%	44,886
European (non-Finnish)	0.00178%	56,189
Admixed American	0.00167%	60,020

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.Ser301Phe
Coding: c.902C>T
MANE Select: NM_001371986
dbSNP: rs564175384
Type: single nucleotide variant
Location: chr2:209793823 (GRCh38)
Gene constraint: LOEUF 0.48 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 301: the 'disordered' region

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

Similar variants

UNC80 p.Ser301= 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
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-ser301phe (accessed [today's date]).

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