Is TRIM59 p.Ser339Pro (c.1015T>C) pathogenic?

TRIM59 p.Ser339Pro (c.1015T>C) is classified Uncertain significance in TRIM59 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-29). AlphaMissense: likely benign (0.2584); Very rare (popmax 0.00017%, nfe).

How common is TRIM59 p.Ser339Pro (c.1015T>C) in the general population?

TRIM59 p.Ser339Pro (c.1015T>C) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about TRIM59 p.Ser339Pro (c.1015T>C)?

AlphaMissense predicts likely benign (score 0.2584) — an in-silico prediction, not a clinical call.

TRIM59 p.Ser339Pro

c.1015T>C · rs1484437579 · VCV2531497

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2584 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2584	likely benign
REVEL	0.162	moderately benign-leaning
SaProt	LLR -9.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 1.4, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 1,208 bp · p 0.72 · regional, not allelic
Overall
CADD	22.2	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 0.00017% European (non-Finnish) · 2/1,179,352 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,612,212 alleles · very rare exomes 0/1,459,970 · genomes 2/152,242 · 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: TRIM59
Protein: p.Ser339Pro
Coding: c.1015T>C
MANE Select: NM_173084
dbSNP: rs1484437579
Type: single nucleotide variant
Location: chr3:160438169 (GRCh38)
Gene constraint: LOEUF 0.675 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 84.52

Full TRIM59 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TRIM59 p.Arg21His Uncertain significance ★ ⚠ same type
TRIM59 p.Arg60Gly Uncertain significance ★ ⚠ same type
TRIM59 p.Asn215Tyr Uncertain significance ★ ⚠ same type
TRIM59 p.Asn377Ser Uncertain significance ★ ⚠ same type
TRIM59 p.Asn384Ser Uncertain significance ★ ⚠ same type
TRIM59 p.Asp181Tyr Uncertain significance ★ ⚠ same type
TRIM59 p.Asp209Gly Uncertain significance ★ ⚠ same type
TRIM59 p.Cys109Arg 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/trim59-p-ser339pro (accessed [today's date]).

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