Is AGPS p.Ala7Val (c.20C>T) pathogenic?

AGPS p.Ala7Val (c.20C>T) is classified Conflicting classifications of pathogenicity in AGPS (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-05-06). AlphaMissense: likely benign (0.2495); Rare (popmax 0.159%, afr).

How common is AGPS p.Ala7Val (c.20C>T) in the general population?

AGPS p.Ala7Val (c.20C>T) is rare (popmax 0.159%, afr) (gnomAD).

What do computational predictors say about AGPS p.Ala7Val (c.20C>T)?

AlphaMissense predicts likely benign (score 0.2495) — an in-silico prediction, not a clinical call.

AGPS p.Ala7Val

c.20C>T · rs539573652 · VCV383646

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2495 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.159%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2495	likely benign
REVEL	0.305	indeterminate
SaProt	LLR -8.45	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 0.061	GERP 1.8, phastCons 0.54
Regional constraint	o/e 1.09	unconstrained · MANE · 244 bp · p 0.32 · regional, not allelic
Overall
CADD	22.5	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 0.159% African / African-American · 111/69,694 alleles

Filtering AF 0.135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.126%

Overall 0.00917% 139/1,515,806 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.159%	628
Remaining individualsnot grpmax-eligible	0.0154%	6,494
Admixed American	0.00656%	15,239
South Asian	0.00257%	38,842
European (non-Finnish)	0.00122%	81,704

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.Ala7Val
Coding: c.20C>T
MANE Select: NM_003659
dbSNP: rs539573652
Type: single nucleotide variant
Location: chr2:177392809 (GRCh38)
Gene constraint: LOEUF 0.408 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 89.27
Residue 7: the 'disordered' region

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

Similar variants

AGPS p.Arg182Ter Pathogenic/Likely pathogenic ★★ same type
AGPS p.Thr309Ile Likely pathogenic ★★ same type
AGPS c.1855+6C>A Uncertain significance ★★ same type
AGPS c.*118A>G Uncertain significance ★★ same type
AGPS p.Arg265Gln Uncertain significance ★★ ⚠ same type
AGPS p.Asn649Ser Uncertain significance ★★ ⚠ same type
AGPS p.Asp28Val Uncertain significance ★★ ⚠ same type
AGPS p.Asp590His 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/agps-p-ala7val (accessed [today's date]).

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