Is ANXA7 p.Ile166Val (c.496A>G) pathogenic?

ANXA7 p.Ile166Val (c.496A>G) is classified Uncertain significance in ANXA7 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-05-26). AlphaMissense: likely benign (0.0583); Ultra-rare (popmax 0.029%, eas).

How common is ANXA7 p.Ile166Val (c.496A>G) in the general population?

ANXA7 p.Ile166Val (c.496A>G) is ultra-rare (popmax 0.029%, eas) (gnomAD).

What do computational predictors say about ANXA7 p.Ile166Val (c.496A>G)?

AlphaMissense predicts likely benign (score 0.0583) — an in-silico prediction, not a clinical call.

ANXA7 p.Ile166Val

c.496A>G · VCV3299766

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0583 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0583	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -4.82	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 0.008	GERP -4.1, phastCons 0.13
Regional constraint	o/e 0.94	unconstrained · MANE · 25 kb · p 0.16 · regional, not allelic
Overall
CADD	14.84	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM I188V vs ClinVar I166V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.029% East Asian · 13/44,880 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00477% 77/1,614,106 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.029%	3,452
Finnishnot grpmax-eligible	0.0156%	6,403
European (non-Finnish)	0.00424%	23,599
Admixed American	0.00167%	60,016
Remaining individualsnot grpmax-eligible	0.0016%	62,504
African / African-American	0.00133%	75,080
South Asian	0.0011%	91,072

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: ANXA7
Protein: p.Ile166Val
Coding: c.496A>G
MANE Select: NM_001156
Type: single nucleotide variant
Location: chr10:73388354 (GRCh38)
Gene constraint: LOEUF 1.055 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.67 · 1 PDB

Full ANXA7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANXA7 c.1089+1G>T Likely pathogenic ★ same type
ANXA7 c.435+423C>G Uncertain significance ★ ⚠ same type
ANXA7 c.435+429C>T Uncertain significance ★ ⚠ same type
ANXA7 c.435+444T>C Uncertain significance ★ ⚠ same type
ANXA7 c.435+450C>T Uncertain significance ★ ⚠ same type
ANXA7 c.435+452G>A Uncertain significance ★ ⚠ same type
ANXA7 c.435+459T>C Uncertain significance ★ ⚠ same type
ANXA7 p.Ala160Asp 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/anxa7-p-ile166val (accessed [today's date]).

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