Is ANG p.Leu9Phe (c.27G>T) pathogenic?

ANG p.Leu9Phe (c.27G>T) is classified Uncertain significance in ANG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-18). AlphaMissense: likely benign (0.0694); Absent from gnomAD v4.1.

How common is ANG p.Leu9Phe (c.27G>T) in the general population?

ANG p.Leu9Phe (c.27G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANG p.Leu9Phe (c.27G>T)?

AlphaMissense predicts likely benign (score 0.0694) — an in-silico prediction, not a clinical call.

ANG p.Leu9Phe

c.27G>T · VCV4746198

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0694 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0694	likely benign
REVEL	0.271	benign-leaning
SaProt	LLR -7.87	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 0.03	GERP -2.9, phastCons 0.004
Regional constraint	o/e 0.95	unconstrained · MANE · 440 bp · p 0.49 · regional, not allelic
Overall
CADD	13.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ANG
Protein: p.Leu9Phe
Coding: c.27G>T
MANE Select: NM_001097577
Type: single nucleotide variant
Location: chr14:20693591 (GRCh38)
Gene constraint: LOEUF 1.697 · pLI 0.42 (gnomAD)
Structure: AlphaFold pLDDT 90.50 · 56 PDB

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-leu9phe (accessed [today's date]).

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