Is ANG p.Ala122= (c.366G>A) pathogenic?

ANG p.Ala122= (c.366G>A) is classified Likely benign in ANG (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-01). Very rare (popmax 0.0022%, sas).

How common is ANG p.Ala122= (c.366G>A) in the general population?

ANG p.Ala122= (c.366G>A) is very rare (popmax 0.0022%, sas) (gnomAD).

ANG p.Ala122=

c.366G>A · VCV4822596

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4	GERP -3.2
Overall
CADD	0.355	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,030 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000684% 10/1,461,856 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,515
Admixed American	0.00167%	60,020
European (non-Finnish)	0.000593%	168,574

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: ANG
Protein: p.Ala122=
Coding: c.366G>A
MANE Select: NM_001097577
Type: single nucleotide variant
Location: chr14:20693930 (GRCh38)
Gene constraint: LOEUF 1.697 · pLI 0.42 (gnomAD)
Structure: AlphaFold pLDDT 90.50 · 56 PDB
Residue 122: a disulfide bond; a β-strand

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

Similar variants

ANG p.Arg75His Uncertain significance ★★ ⚠ same type
ANG p.Gly123Ala Uncertain significance ★★ ⚠ same type
ANG p.Gly15Ser Uncertain significance ★★ ⚠ same type
ANG p.Lys78Glu Uncertain significance ★★ ⚠ same type
ANG p.Pro21Leu Uncertain significance ★★ ⚠ same type
ANG p.Pro21Ser Uncertain significance ★★ ⚠ same type
ANG c.-18-222G>C Benign ★★ same type
ANG c.-237A>C Benign ★★ 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/ang-p-ala122 (accessed [today's date]).

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