Is ANG p.Phe33= (c.99C>T) pathogenic?

ANG p.Phe33= (c.99C>T) is classified Benign/Likely benign in ANG (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-21). Rare (popmax 0.725%, sas); Associated with amyotrophic lateral sclerosis type 9.

What condition is associated with ANG p.Phe33= (c.99C>T)?

ANG p.Phe33= (c.99C>T) is associated with amyotrophic lateral sclerosis type 9 (ClinVar).

How common is ANG p.Phe33= (c.99C>T) in the general population?

ANG p.Phe33= (c.99C>T) is rare (popmax 0.725%, sas) (gnomAD).

ANG p.Phe33=

c.99C>T · rs563139057 · VCV312773

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.725%, sas)

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 0.83	GERP 0.48, phastCons 1
Overall
CADD	12.86	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.725% South Asian · 660/91,082 alleles

Filtering AF 0.679% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.661%

Overall 0.0436% 703/1,614,144 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.725%	138
Remaining individualsnot grpmax-eligible	0.064%	1,563
Middle Eastern	0.0165%	6,062
African / African-American	0.00133%	75,024
European (non-Finnish)	8.47e-05%	1,180,026

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.Phe33=
Coding: c.99C>T
MANE Select: NM_002937 · reported on NM_001097577
dbSNP: rs563139057
Type: single nucleotide variant
Location: chr14:20693663 (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-phe33 (accessed [today's date]).

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