Is YIPF5 p.Asp43Asn (c.127G>A) pathogenic?

YIPF5 p.Asp43Asn (c.127G>A) is classified Uncertain significance in YIPF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-01). AlphaMissense: likely benign (0.1278); Absent from gnomAD v4.1.

How common is YIPF5 p.Asp43Asn (c.127G>A) in the general population?

YIPF5 p.Asp43Asn (c.127G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about YIPF5 p.Asp43Asn (c.127G>A)?

AlphaMissense predicts likely benign (score 0.1278) — an in-silico prediction, not a clinical call.

YIPF5 p.Asp43Asn

c.127G>A · VCV3983144

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1278 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1278	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -8.12	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.7	GERP 2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 9,555 bp · p 0.25 · regional, not allelic
Overall
CADD	21.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: YIPF5
Protein: p.Asp43Asn
Coding: c.127G>A
MANE Select: NM_030799
Type: single nucleotide variant
Location: chr5:144165588 (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.Asp43Val Uncertain significance ★ ⚠ same residue
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.Cys179Phe Uncertain significance ★ ⚠ same type
YIPF5 p.Gln21Arg Uncertain significance ★ ⚠ same type
YIPF5 p.Glu94Asp 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-asp43asn (accessed [today's date]).

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