Is ANG p.Thr121= (c.363A>T) pathogenic?

ANG p.Thr121= (c.363A>T) is classified Benign/Likely benign in ANG (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-01). Low-frequency (popmax 4.5%, afr); Associated with amyotrophic lateral sclerosis type 9.

What condition is associated with ANG p.Thr121= (c.363A>T)?

ANG p.Thr121= (c.363A>T) is associated with amyotrophic lateral sclerosis type 9 (ClinVar).

How common is ANG p.Thr121= (c.363A>T) in the general population?

ANG p.Thr121= (c.363A>T) is low-frequency (popmax 4.5%, afr) (gnomAD).

ANG p.Thr121=

c.363A>T · rs2228653 · VCV312775

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.5%, afr)

Conditions

amyotrophic lateral sclerosis type 9

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -5.2	GERP -3.2
Overall
CADD	0.183	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.5% African / African-American · 3,375/75,014 alleles

Filtering AF 4.37% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.32%

Overall 0.296% 4,780/1,614,146 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.5%	22
Middle Eastern	0.775%	129
Admixed American	0.64%	156
Remaining individualsnot grpmax-eligible	0.491%	204
Ashkenazi Jewishnot grpmax-eligible	0.135%	740
European (non-Finnish)	0.0514%	1,944
South Asian	0.022%	4,554

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.Thr121=
Coding: c.363A>T
dbSNP: rs2228653
Type: single nucleotide variant
Location: chr14:20693927 (GRCh38)

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

Disease context

amyotrophic lateral sclerosis type 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-thr121 (accessed [today's date]).

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