Is YIPF5 p.Thr63Ala (c.187A>G) pathogenic?

YIPF5 p.Thr63Ala (c.187A>G) is classified Uncertain significance in YIPF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-07). AlphaMissense: likely benign (0.0916); Very rare (popmax 0.00254%, nfe).

How common is YIPF5 p.Thr63Ala (c.187A>G) in the general population?

YIPF5 p.Thr63Ala (c.187A>G) is very rare (popmax 0.00254%, nfe) (gnomAD).

What do computational predictors say about YIPF5 p.Thr63Ala (c.187A>G)?

AlphaMissense predicts likely benign (score 0.0916) — an in-silico prediction, not a clinical call.

YIPF5 p.Thr63Ala

c.187A>G · VCV3471719

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0916 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00254%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0916	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -6.24	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 4.2	GERP 1.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 9,555 bp · p 0.25 · regional, not allelic
Overall
CADD	19.45	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 0.00254% European (non-Finnish) · 30/1,180,036 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00156%

Overall 0.00186% 30/1,614,082 alleles · very rare exomes 29/1,461,864 · genomes 1/152,218 · 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: YIPF5
Protein: p.Thr63Ala
Coding: c.187A>G
MANE Select: NM_030799
Type: single nucleotide variant
Location: chr5:144165528 (GRCh38)
Gene constraint: LOEUF 0.464 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 66.45

Full YIPF5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

YIPF5 p.Val51Ile Uncertain significance ★★ ⚠ same type
YIPF5 p.Ala198Thr Uncertain significance ★ ⚠ same type
YIPF5 p.Ala245Thr Uncertain significance ★ ⚠ same type
YIPF5 p.Asp20Gly Uncertain significance ★ ⚠ same type
YIPF5 p.Asp43Asn Uncertain significance ★ ⚠ same type
YIPF5 p.Asp43Val Uncertain significance ★ ⚠ same type
YIPF5 p.Cys179Phe Uncertain significance ★ ⚠ same type
YIPF5 p.Gln21Arg 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/yipf5-p-thr63ala (accessed [today's date]).

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