Is TRIM59 p.Ile70Phe (c.208A>T) pathogenic?

TRIM59 p.Ile70Phe (c.208A>T) is classified Uncertain significance in TRIM59 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-22). AlphaMissense: likely benign (0.2001); Very rare (popmax 0.01%, amr).

How common is TRIM59 p.Ile70Phe (c.208A>T) in the general population?

TRIM59 p.Ile70Phe (c.208A>T) is very rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about TRIM59 p.Ile70Phe (c.208A>T)?

AlphaMissense predicts likely benign (score 0.2001) — an in-silico prediction, not a clinical call.

TRIM59 p.Ile70Phe

c.208A>T · VCV3973637

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2001 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.01%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2001	likely benign
REVEL	0.446	indeterminate
SaProt	LLR -12.33	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP 0.41, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 1,208 bp · p 0.72 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/60,022 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00041% 6/1,461,782 alleles · very rare

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.Ile70Phe
Coding: c.208A>T
MANE Select: NM_173084
Type: single nucleotide variant
Location: chr3:160438976 (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-ile70phe (accessed [today's date]).

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