Is AGAP6 p.Arg70Trp (c.208C>T) pathogenic?

AGAP6 p.Arg70Trp (c.208C>T) is classified Uncertain significance in AGAP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-09). AlphaMissense: likely benign (0.0889); Ultra-rare (popmax 0.0435%, afr).

How common is AGAP6 p.Arg70Trp (c.208C>T) in the general population?

AGAP6 p.Arg70Trp (c.208C>T) is ultra-rare (popmax 0.0435%, afr) (gnomAD).

What do computational predictors say about AGAP6 p.Arg70Trp (c.208C>T)?

AlphaMissense predicts likely benign (score 0.0889) — an in-silico prediction, not a clinical call.

AGAP6 p.Arg70Trp

c.208C>T · VCV4023047

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0889 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0435%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0889	likely benign
REVEL	0.334	indeterminate
SaProt	LLR -7.93	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 0.11
Regional constraint	o/e 0.64	unconstrained · MANE · 21 kb · p 1.2e-16 · regional, not allelic
Overall
CADD	12.73	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 0.0435% African / African-American · 28/64,340 alleles

Filtering AF 0.0309% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0266%

Overall 0.00259% 41/1,580,468 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0435%	2,298
Remaining individualsnot grpmax-eligible	0.00322%	31,064
Admixed American	0.00169%	59,172
European (non-Finnish)	0.000853%	117,291

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: AGAP6
Protein: p.Arg70Trp
Coding: c.208C>T
MANE Select: NM_001077665
Type: single nucleotide variant
Location: chr10:49988923 (GRCh38)
Gene constraint: LOEUF 0.757 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.73

Full AGAP6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AGAP6 p.Ala105Thr Uncertain significance ★ ⚠ same type
AGAP6 p.Ala109Thr Uncertain significance ★ ⚠ same type
AGAP6 p.Ala135Val Uncertain significance ★ ⚠ same type
AGAP6 p.Ala180Gly Uncertain significance ★ ⚠ same type
AGAP6 p.Ala425Thr Uncertain significance ★ ⚠ same type
AGAP6 p.Ala433Val Uncertain significance ★ ⚠ same type
AGAP6 p.Ala43Ser Uncertain significance ★ ⚠ same type
AGAP6 p.Ala444Pro 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/agap6-p-arg70trp (accessed [today's date]).

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