Is PGD p.Val371Leu (c.1111G>C) pathogenic?

PGD p.Val371Leu (c.1111G>C) is classified Uncertain significance in PGD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-02). AlphaMissense: likely benign (0.33); Very rare (popmax 0.00208%, nfe).

How common is PGD p.Val371Leu (c.1111G>C) in the general population?

PGD p.Val371Leu (c.1111G>C) is very rare (popmax 0.00208%, nfe) (gnomAD).

What do computational predictors say about PGD p.Val371Leu (c.1111G>C)?

AlphaMissense predicts likely benign (score 0.33) — an in-silico prediction, not a clinical call.

PGD p.Val371Leu

c.1111G>C · rs371087028 · VCV2523043

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.33 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00208%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.33	likely benign
REVEL	0.243	benign-leaning
SaProt	LLR -9.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.22	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 9.8	GERP 1.8, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 20 kb · p 1e-07 · regional, not allelic
Overall
CADD	27.3	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

Grpmax group 0.00208% European (non-Finnish) · 23/1,105,110 alleles

Filtering AF 0.00139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00164% 25/1,527,822 alleles · very rare exomes 23/1,377,148 · genomes 2/150,674 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00208%	48,048
Remaining individualsnot grpmax-eligible	0.00168%	59,674
African / African-American	0.00138%	72,504

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: PGD
Protein: p.Val371Leu
Coding: c.1111G>C
MANE Select: NM_002631
dbSNP: rs371087028
Type: single nucleotide variant
Location: chr1:10418827 (GRCh38)
Gene constraint: LOEUF 0.552 · pLI 0.84 (gnomAD)
Structure: AlphaFold pLDDT 96.98 · 4 PDB
Residue 371: an α-helix

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

Similar variants

PGD c.519+2C>T Uncertain significance ★ same type
PGD p.Ala149Gly Uncertain significance ★ ⚠ same type
PGD p.Ala258Val Uncertain significance ★ ⚠ same type
PGD p.Ala336Pro Uncertain significance ★ ⚠ same type
PGD p.Ala345Gly Uncertain significance ★ ⚠ same type
PGD p.Arg407Gln Uncertain significance ★ ⚠ same type
PGD p.Asn354Ser Uncertain significance ★ ⚠ same type
PGD p.Asn354Tyr Uncertain significance ★ ⚠ 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/pgd-p-val371leu (accessed [today's date]).

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