Is ANGPTL7 p.Arg90His (c.269G>A) pathogenic?

ANGPTL7 p.Arg90His (c.269G>A) is classified Uncertain significance in ANGPTL7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-06). AlphaMissense: likely benign (0.0845); Ultra-rare (popmax 0.0223%, eas).

How common is ANGPTL7 p.Arg90His (c.269G>A) in the general population?

ANGPTL7 p.Arg90His (c.269G>A) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

What do computational predictors say about ANGPTL7 p.Arg90His (c.269G>A)?

AlphaMissense predicts likely benign (score 0.0845) — an in-silico prediction, not a clinical call.

ANGPTL7 p.Arg90His

c.269G>A · rs753003549 · VCV2533891

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0845 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0845	likely benign
REVEL	0.072	moderately benign-leaning
SaProt	LLR -7.75	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 3.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 5,440 bp · p 0.58 · regional, not allelic
Overall
CADD	21.2	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0223% East Asian · 10/44,898 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00916%

Overall 0.00136% 22/1,614,076 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0223%	4,490
African / African-American	0.0107%	9,367
European (non-Finnish)	0.000339%	295,008

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: ANGPTL7
Protein: p.Arg90His
Coding: c.269G>A
MANE Select: NM_021146
dbSNP: rs753003549
Type: single nucleotide variant
Location: chr1:11189848 (GRCh38)
Gene constraint: LOEUF 1.231 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.45

Full ANGPTL7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANGPTL7 p.Arg90Cys Uncertain significance ★ ⚠ same residue
ANGPTL7 p.Arg176Ser Uncertain significance ★ ⚠ same type
ANGPTL7 p.Arg211Gln Uncertain significance ★ ⚠ same type
ANGPTL7 p.Arg214Ile Uncertain significance ★ ⚠ same type
ANGPTL7 p.Arg218Gln Uncertain significance ★ ⚠ same type
ANGPTL7 p.Arg220His Uncertain significance ★ ⚠ same type
ANGPTL7 p.Arg231Cys Uncertain significance ★ ⚠ same type
ANGPTL7 p.Arg289Cys 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/angptl7-p-arg90his (accessed [today's date]).

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