Is YIPF5 p.Ala76Val (c.227C>T) pathogenic?

YIPF5 p.Ala76Val (c.227C>T) is classified Benign in YIPF5 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-01). AlphaMissense: likely benign (0.0836); Low-frequency (popmax 2.97%, mid).

How common is YIPF5 p.Ala76Val (c.227C>T) in the general population?

YIPF5 p.Ala76Val (c.227C>T) is low-frequency (popmax 2.97%, mid) (gnomAD).

What do computational predictors say about YIPF5 p.Ala76Val (c.227C>T)?

AlphaMissense predicts likely benign (score 0.0836) — an in-silico prediction, not a clinical call.

YIPF5 p.Ala76Val

c.227C>T · rs35429531 · VCV2655875

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0836 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.97%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0836	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -7.05	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 4.8	GERP 1.9, phastCons 0.96
Regional constraint	o/e 0.93	unconstrained · MANE · 9,555 bp · p 0.25 · regional, not allelic
Overall
CADD	16.97	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 2.97% Middle Eastern · 180/6,060 alleles

Filtering AF 2.62% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.53%

Overall 2.1% 33,926/1,614,122 alleles · low-frequency exomes 31,662/1,461,846 · genomes 2,264/152,276 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	2.97%	34
European (non-Finnish)	2.57%	39
Remaining individualsnot grpmax-eligible	1.68%	60
Ashkenazi Jewishnot grpmax-eligible	1.15%	87
Finnishnot grpmax-eligible	0.964%	104
Admixed American	0.9%	111
South Asian	0.639%	157
African / African-American	0.449%	223
Amishnot grpmax-eligible	0.219%	456
East Asian	0.00223%	44,872

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.Ala76Val
Coding: c.227C>T
MANE Select: NM_030799
dbSNP: rs35429531
Type: single nucleotide variant
Location: chr5:144165488 (GRCh38)
Gene constraint: LOEUF 0.464 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 66.45
Residue 76: the 'interaction with sec23' region

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-ala76val (accessed [today's date]).

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