Is VASP p.Arg68Pro (c.203G>C) pathogenic?

VASP p.Arg68Pro (c.203G>C) is classified Uncertain significance in VASP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-29). AlphaMissense: likely pathogenic (0.6028); Very rare (popmax 0.00177%, amr).

How common is VASP p.Arg68Pro (c.203G>C) in the general population?

VASP p.Arg68Pro (c.203G>C) is very rare (popmax 0.00177%, amr) (gnomAD).

What do computational predictors say about VASP p.Arg68Pro (c.203G>C)?

AlphaMissense predicts likely pathogenic (score 0.6028) — an in-silico prediction, not a clinical call.

VASP p.Arg68Pro

c.203G>C · VCV4198397

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6028 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00177%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6028	likely pathogenic
REVEL	0.251	benign-leaning
SaProt	LLR -8.94	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.6	GERP -4, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 14 kb · p 0.00082 · regional, not allelic
Overall
CADD	25.9	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 0.00177% Admixed American · 1/56,566 alleles

Overall 0.000217% 3/1,380,712 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00177%	56,566
Remaining individualsnot grpmax-eligible	0.00176%	56,788
European (non-Finnish)	8.89e-05%	1,125,066

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: VASP
Protein: p.Arg68Pro
Coding: c.203G>C
MANE Select: NM_003370
Type: single nucleotide variant
Location: chr19:45517954 (GRCh38)
Gene constraint: LOEUF 0.746 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.43 · 11 PDB
Residue 68: the wh1 domain

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

Similar variants

VASP p.Arg68Gln Uncertain significance ★ ⚠ same residue
VASP p.Arg68Trp Uncertain significance ★ ⚠ same residue
VASP p.Ala104Thr Benign ★★ same type
VASP p.Ala112Val Uncertain significance ★ ⚠ same type
VASP p.Arg10Gln Uncertain significance ★ ⚠ same type
VASP p.Arg22Gln Uncertain significance ★ ⚠ same type
VASP p.Arg377Gln Uncertain significance ★ ⚠ same type
VASP p.Asn45Lys 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/vasp-p-arg68pro (accessed [today's date]).

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