Is PGD p.Val410Ile (c.1228G>A) pathogenic?

PGD p.Val410Ile (c.1228G>A) is classified Likely benign in PGD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-02). AlphaMissense: likely benign (0.0955); Very rare (popmax 0.00668%, eas).

How common is PGD p.Val410Ile (c.1228G>A) in the general population?

PGD p.Val410Ile (c.1228G>A) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about PGD p.Val410Ile (c.1228G>A)?

AlphaMissense predicts likely benign (score 0.0955) — an in-silico prediction, not a clinical call.

PGD p.Val410Ile

c.1228G>A · rs759462109 · VCV3211781

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0955 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0955	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -8.36	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 0.36	GERP -2, phastCons 0.003
Regional constraint	o/e 0.77	unconstrained · MANE · 20 kb · p 1e-07 · regional, not allelic
Overall
CADD	13.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,894 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00031% 5/1,613,802 alleles · very rare exomes 4/1,461,594 · genomes 1/152,208 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,965
Remaining individualsnot grpmax-eligible	0.0016%	62,478
European (non-Finnish)	8.47e-05%	1,180,008

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.Val410Ile
Coding: c.1228G>A
MANE Select: NM_002631
dbSNP: rs759462109
Type: single nucleotide variant
Location: chr1:10419435 (GRCh38)
Gene constraint: LOEUF 0.552 · pLI 0.84 (gnomAD)
Structure: AlphaFold pLDDT 96.98 · 4 PDB
Residue 410: 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-val410ile (accessed [today's date]).

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