Is ARFIP2 p.Val122Met (c.364G>A) pathogenic?

ARFIP2 p.Val122Met (c.364G>A) is classified Uncertain significance in ARFIP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-11). AlphaMissense: likely pathogenic (0.6917); Very rare (popmax 0.00133%, afr).

How common is ARFIP2 p.Val122Met (c.364G>A) in the general population?

ARFIP2 p.Val122Met (c.364G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ARFIP2 p.Val122Met (c.364G>A)?

AlphaMissense predicts likely pathogenic (score 0.6917) — an in-silico prediction, not a clinical call.

ARFIP2 p.Val122Met

c.364G>A · rs772069696 · VCV2232440

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6917 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6917	likely pathogenic
REVEL	0.796	moderately pathogenic-leaning
SaProt	LLR -9.52	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 1,624 bp · p 0.00026 · regional, not allelic
Overall
CADD	28.4	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 0.00133% African / African-American · 1/75,038 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000274% 4/1,461,882 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,038
South Asian	0.0011%	91,088
European (non-Finnish)	0.000169%	590,019

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: ARFIP2
Protein: p.Val122Met
Coding: c.364G>A
MANE Select: NM_001376558
dbSNP: rs772069696
Type: single nucleotide variant
Location: chr11:6478911 (GRCh38)
Gene constraint: LOEUF 0.543 · pLI 0.90 (gnomAD)
Structure: AlphaFold pLDDT 81.84 · 5 PDB
Residue 122: the ah domain

Full ARFIP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARFIP2 c.197-16G>A Uncertain significance ★ same type
ARFIP2 c.197-75G>A Uncertain significance ★ same type
ARFIP2 c.197-76A>G Uncertain significance ★ same type
ARFIP2 c.197-87C>T Uncertain significance ★ same type
ARFIP2 p.Ala252Ser Uncertain significance ★ ⚠ same type
ARFIP2 p.Arg138His Uncertain significance ★ ⚠ same type
ARFIP2 p.Arg148Gln Uncertain significance ★ ⚠ same type
ARFIP2 p.Arg269Trp 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/arfip2-p-val122met (accessed [today's date]).

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