Is UNC119 p.Ser78Pro (c.232T>C) pathogenic?

UNC119 p.Ser78Pro (c.232T>C) is classified Uncertain significance in UNC119 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-18). AlphaMissense: likely benign (0.2904); Very rare (popmax 8.48e-05%, nfe).

How common is UNC119 p.Ser78Pro (c.232T>C) in the general population?

UNC119 p.Ser78Pro (c.232T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about UNC119 p.Ser78Pro (c.232T>C)?

AlphaMissense predicts likely benign (score 0.2904) — an in-silico prediction, not a clinical call.

UNC119 p.Ser78Pro

c.232T>C · rs2070239676 · VCV2112415

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2904 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2904	likely benign
REVEL	0.35	indeterminate
SaProt	LLR -8.77	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP -0.37, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 5,257 bp · p 0.44 · regional, not allelic
Overall
CADD	22.0	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 and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,756 alleles

Overall 6.2e-05% 1/1,613,782 alleles · very rare exomes 1/1,461,486 · genomes 0/152,296 · joint denominator

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: UNC119
Protein: p.Ser78Pro
Coding: c.232T>C
MANE Select: NM_005148
dbSNP: rs2070239676
Type: single nucleotide variant
Location: chr17:28548694 (GRCh38)
Gene constraint: LOEUF 1.139 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.03 · 9 PDB
Residue 78: a UniProt-annotated variant site (in cord24; when expressed in transgenic mice, it results in age-dependent fundus lesions, defects in photoreceptor synaptic transmission and retinal degeneration)

Full UNC119 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

UNC119 p.Ser78Tyr Uncertain significance ★ same residue
UNC119 p.Ser78= Likely benign ★ same residue
UNC119 p.Arg113Trp Uncertain significance ★★ ⚠ same type
UNC119 p.Arg118Gln Uncertain significance ★★ ⚠ same type
UNC119 p.Arg118Trp Uncertain significance ★★ ⚠ same type
UNC119 p.Arg119Trp Uncertain significance ★★ ⚠ same type
UNC119 p.Arg127Cys Uncertain significance ★★ ⚠ same type
UNC119 p.Arg127His Uncertain significance ★★ ⚠ 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/unc119-p-ser78pro (accessed [today's date]).

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