Is UNC79 p.Pro175= (c.525C>T) pathogenic?

UNC79 p.Pro175= (c.525C>T) is classified Benign in UNC79 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-01). Rare (popmax 0.281%, mid).

How common is UNC79 p.Pro175= (c.525C>T) in the general population?

UNC79 p.Pro175= (c.525C>T) is rare (popmax 0.281%, mid) (gnomAD).

UNC79 p.Pro175=

c.525C>T · VCV4533616

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.281%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.1	GERP 1.6, phastCons 1
Overall
CADD	13.33	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.281% Middle Eastern · 17/6,056 alleles

Filtering AF 0.179% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.164%

Overall 0.194% 3,135/1,613,098 alleles · rare exomes 2,792/1,460,878 · genomes 343/152,220 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.41%	71
Middle Easterngrpmax	0.281%	356
Remaining individualsnot grpmax-eligible	0.186%	539
European (non-Finnish)	0.173%	579
South Asian	0.0472%	2,117
Admixed American	0.025%	3,996
African / African-American	0.0107%	9,376
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,797
East Asian	0.00223%	44,788

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: UNC79
Protein: p.Pro175=
Coding: c.525C>T
MANE Select: NM_001395159
Type: single nucleotide variant
Location: chr14:93477634 (GRCh38)
Gene constraint: LOEUF 0.168 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.95 · 3 PDB

Full UNC79 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

UNC79 p.Ile1680Thr Uncertain significance ★★ same type
UNC79 p.Pro2467Arg Uncertain significance ★★ same type
UNC79 p.Ser1741Cys Uncertain significance ★★ same type
UNC79 p.Ser706Arg Uncertain significance ★★ same type
UNC79 p.Thr2409Met Uncertain significance ★★ same type
UNC79 p.Tyr539Phe Uncertain significance ★★ same type
UNC79 c.3191-2A>C Likely pathogenic ★ same type
UNC79 c.6134-1G>A 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/unc79-p-pro175 (accessed [today's date]).

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