Is ANG p.Phe12= (c.36C>T) pathogenic?

ANG p.Phe12= (c.36C>T) is classified Likely benign in ANG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-14). Very rare (popmax 0.01%, amr); Associated with Inborn genetic diseases.

What condition is associated with ANG p.Phe12= (c.36C>T)?

ANG p.Phe12= (c.36C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ANG p.Phe12= (c.36C>T) in the general population?

ANG p.Phe12= (c.36C>T) is very rare (popmax 0.01%, amr) (gnomAD).

ANG p.Phe12=

c.36C>T · rs756615766 · VCV3220948

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.01%, amr)

Conditions

Inborn genetic diseases

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 0.96	GERP 0.48, phastCons 0.49
Overall
CADD	16.63	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/60,028 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000889% 13/1,461,510 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	10,005
Remaining individualsnot grpmax-eligible	0.0032%	31,240
African / African-American	0.00267%	37,508
European (non-Finnish)	0.000254%	393,345

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.Phe12=
Coding: c.36C>T
MANE Select: NM_001097577
dbSNP: rs756615766
Type: single nucleotide variant
Location: chr14:20693600 (GRCh38)
Gene constraint: LOEUF 1.697 · pLI 0.42 (gnomAD)
Structure: AlphaFold pLDDT 90.50 · 56 PDB
Residue 12: a UniProt-annotated variant site (in als9)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ANG p.Gly123Ala Uncertain significance ★★ ⚠ same condition
ANG p.Gly15Ser Uncertain significance ★★ ⚠ same condition
ANG p.Gly110= Benign/Likely benign ★★ same condition
ANG p.Gly44= Benign/Likely benign ★★ same condition
ANG p.Ala120Asp Uncertain significance ★ ⚠ same condition
ANG p.His32Gln Uncertain significance ★ ⚠ same condition
ANG p.His71Asn Uncertain significance ★ ⚠ same condition
ANG p.Pro114Thr Uncertain significance ★ ⚠ same condition

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-phe12 (accessed [today's date]).

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