Is YIPF5 p.Ala181Val (c.542C>T) pathogenic?

YIPF5 p.Ala181Val (c.542C>T) is classified Pathogenic in YIPF5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-04-16). AlphaMissense: likely pathogenic (0.6595); Absent from gnomAD v4.1; Associated with microcephaly, epilepsy, and diabetes syndrome 2.

What condition is associated with YIPF5 p.Ala181Val (c.542C>T)?

YIPF5 p.Ala181Val (c.542C>T) is associated with microcephaly, epilepsy, and diabetes syndrome 2 (ClinVar).

How common is YIPF5 p.Ala181Val (c.542C>T) in the general population?

YIPF5 p.Ala181Val (c.542C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about YIPF5 p.Ala181Val (c.542C>T)?

AlphaMissense predicts likely pathogenic (score 0.6595) — an in-silico prediction, not a clinical call.

YIPF5 p.Ala181Val

c.542C>T · rs1752071425 · VCV1064542

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6595 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microcephaly, epilepsy, and diabetes syndrome 2

Computational evidence

Protein change
AlphaMissense	0.6595	likely pathogenic ✓ concordant with ClinVar
REVEL	0.164	moderately benign-leaning
SaProt	LLR -7.66	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	Δ0.64	donor gain · deltas
Pangolin	Δ0.42	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 9,555 bp · p 0.25 · regional, not allelic
Overall
CADD	31.0	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

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.Ala181Val
Coding: c.542C>T
MANE Select: NM_030799
dbSNP: rs1752071425
Type: single nucleotide variant
Location: chr5:144162287 (GRCh38)
Gene constraint: LOEUF 0.464 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 66.45
Residue 181: a UniProt-annotated variant site (in meds2; uncertain significance)

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

Disease context

microcephaly, epilepsy, and diabetes syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

YIPF5 p.Val175Asp Uncertain significance ★ ⚠ same condition
YIPF5 p.Trp218Arg Pathogenic same condition
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

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-ala181val (accessed [today's date]).

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