Is AGPS p.Val402Ile (c.1204G>A) pathogenic?

AGPS p.Val402Ile (c.1204G>A) is classified Conflicting classifications of pathogenicity in AGPS (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-10-22). AlphaMissense: likely benign (0.1298); Ultra-rare (popmax 0.0672%, mid); Associated with Inborn genetic diseases.

What condition is associated with AGPS p.Val402Ile (c.1204G>A)?

AGPS p.Val402Ile (c.1204G>A) is associated with Inborn genetic diseases, rhizomelic chondrodysplasia punctata type 3 (ClinVar).

How common is AGPS p.Val402Ile (c.1204G>A) in the general population?

AGPS p.Val402Ile (c.1204G>A) is ultra-rare (popmax 0.0672%, mid) (gnomAD).

What do computational predictors say about AGPS p.Val402Ile (c.1204G>A)?

AlphaMissense predicts likely benign (score 0.1298) — an in-silico prediction, not a clinical call.

AGPS p.Val402Ile

c.1204G>A · rs201282509 · VCV2075066

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1298 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0672%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1298	likely benign
REVEL	0.442	indeterminate
SaProt	LLR -8.88	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 145 kb · p 9.9e-28 · regional, not allelic
Overall
CADD	26.4	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 0.0672% Middle Eastern · 4/5,950 alleles

Filtering AF 0.0263% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0223%

Overall 0.00531% 85/1,599,900 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0672%	1,487
Admixed American	0.0385%	2,594
Ashkenazi Jewishnot grpmax-eligible	0.00685%	14,591
Remaining individualsnot grpmax-eligible	0.00649%	15,417
European (non-Finnish)	0.00435%	22,966
South Asian	0.00111%	90,166

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: AGPS
Protein: p.Val402Ile
Coding: c.1204G>A
MANE Select: NM_003659
dbSNP: rs201282509
Type: single nucleotide variant
Location: chr2:177482157 (GRCh38)
Gene constraint: LOEUF 0.408 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.27

Full AGPS 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

Also linked: rhizomelic chondrodysplasia punctata type 3

Similar variants

AGPS p.Arg182Ter Pathogenic/Likely pathogenic ★★ same condition
AGPS p.Thr309Ile Likely pathogenic ★★ same condition
AGPS c.1855+6C>A Uncertain significance ★★ same condition
AGPS c.*118A>G Uncertain significance ★★ same condition
AGPS p.Arg265Gln Uncertain significance ★★ ⚠ same condition
AGPS p.Asn649Ser Uncertain significance ★★ ⚠ same condition
AGPS p.Asp28Val Uncertain significance ★★ ⚠ same condition
AGPS p.Asp590His 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/agps-p-val402ile (accessed [today's date]).

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