Is YIPF5 p.Ala245Thr (c.733G>A) pathogenic?

YIPF5 p.Ala245Thr (c.733G>A) is classified Uncertain significance in YIPF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-02). AlphaMissense: ambiguous (0.4303); Very rare (popmax 0.00223%, eas).

How common is YIPF5 p.Ala245Thr (c.733G>A) in the general population?

YIPF5 p.Ala245Thr (c.733G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about YIPF5 p.Ala245Thr (c.733G>A)?

AlphaMissense predicts ambiguous (score 0.4303) — an in-silico prediction, not a clinical call.

YIPF5 p.Ala245Thr

c.733G>A · rs902298729 · VCV3191525

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4303 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4303	ambiguous
REVEL	0.22	benign-leaning
SaProt	LLR -10.63	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 9,555 bp · p 0.25 · regional, not allelic
Overall
CADD	28.2	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 0.00223% East Asian · 1/44,870 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.00105% 17/1,613,938 alleles · very rare exomes 15/1,461,824 · genomes 2/152,114 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,870
South Asian	0.0022%	45,537
African / African-American	0.00134%	74,892
European (non-Finnish)	0.0011%	90,770

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.Ala245Thr
Coding: c.733G>A
MANE Select: NM_030799
dbSNP: rs902298729
Type: single nucleotide variant
Location: chr5:144160438 (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.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
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-ala245thr (accessed [today's date]).

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