Is YIPF5 p.Met1Val (c.1A>G) pathogenic?

YIPF5 p.Met1Val (c.1A>G) is classified Uncertain significance in YIPF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). Very rare (popmax 0.00329%, sas).

How common is YIPF5 p.Met1Val (c.1A>G) in the general population?

YIPF5 p.Met1Val (c.1A>G) is very rare (popmax 0.00329%, sas) (gnomAD).

YIPF5 p.Met1Val

c.1A>G · rs1314864442 · VCV2498985

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function in a LoF-intolerant gene
REVEL	0.422	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.8, phastCons 1
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,060 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000558% 9/1,613,302 alleles · very rare exomes 9/1,460,964 · genomes 0/152,338 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,353
European (non-Finnish)	0.000509%	196,535

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.Met1Val
Coding: c.1A>G
MANE Select: NM_030799
dbSNP: rs1314864442
Type: single nucleotide variant
Location: chr5:144169955 (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-met1val (accessed [today's date]).

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