Is PGR p.Ala407Val (c.1220C>T) pathogenic?

PGR p.Ala407Val (c.1220C>T) is classified Uncertain significance in PGR (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-24). AlphaMissense: likely benign (0.1281); No allele count reported in gnomAD v4.1 (AN 1,591,906).

How common is PGR p.Ala407Val (c.1220C>T) in the general population?

PGR p.Ala407Val (c.1220C>T) is no allele count reported in gnomAD v4.1 (AN 1,591,906) (gnomAD).

What do computational predictors say about PGR p.Ala407Val (c.1220C>T)?

AlphaMissense predicts likely benign (score 0.1281) — an in-silico prediction, not a clinical call.

PGR p.Ala407Val

c.1220C>T · VCV4135420

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1281 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,591,906)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1281	likely benign
REVEL	0.103	moderately benign-leaning
SaProt	LLR -7.78	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 7.9	phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 2,957 bp · p 0.00013 · regional, not allelic
Overall
CADD	21.9	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

No allele count reported in gnomAD v4.1 (AN 1,591,906). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PGR
Protein: p.Ala407Val
Coding: c.1220C>T
MANE Select: NM_000926
Type: single nucleotide variant
Location: chr11:101127851 (GRCh38)
Gene constraint: LOEUF 0.554 · pLI 0.72 (gnomAD)
Structure: AlphaFold pLDDT 57.66 · 21 PDB
Residue 407: the 'modulating, pro-rich' region

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

Similar variants

PGR p.Arg187= Benign ★★ same type
PGR p.Arg623= Benign ★★ same type
PGR p.Cys347Ser Benign ★★ same type
PGR p.Gln536Pro Benign ★★ same type
PGR p.Gln75Lys Likely benign ★★ same type
PGR p.Gln868= Benign ★★ same type
PGR p.Gly263= Benign ★★ same type
PGR p.Gly435= Likely 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/pgr-p-ala407val (accessed [today's date]).

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