Is AARD p.Val71Ala (c.212T>C) pathogenic?

AARD p.Val71Ala (c.212T>C) is classified Uncertain significance in AARD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-26). AlphaMissense: likely benign (0.1546); Very rare (popmax 0.00145%, nfe).

How common is AARD p.Val71Ala (c.212T>C) in the general population?

AARD p.Val71Ala (c.212T>C) is very rare (popmax 0.00145%, nfe) (gnomAD).

What do computational predictors say about AARD p.Val71Ala (c.212T>C)?

AlphaMissense predicts likely benign (score 0.1546) — an in-silico prediction, not a clinical call.

AARD p.Val71Ala

c.212T>C · rs1429736696 · VCV2257439

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1546 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00145%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1546	likely benign
REVEL	0.004	strongly benign-leaning
SaProt	LLR -6.44	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 -3.6	GERP -2.5
Regional constraint	o/e 1.12	unconstrained · MANE · 4,454 bp · p 0.076 · regional, not allelic
Overall
CADD	3.522	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 0.00145% European (non-Finnish) · 17/1,174,838 alleles

Filtering AF 0.000881% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000721%

Overall 0.00106% 17/1,601,098 alleles · very rare

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: AARD
Protein: p.Val71Ala
Coding: c.212T>C
MANE Select: NM_001025357
dbSNP: rs1429736696
Type: single nucleotide variant
Location: chr8:116938455 (GRCh38)
Gene constraint: LOEUF 1.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.24

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

Similar variants

AARD p.Ala70= Benign ★★ same type
AARD p.Ala82Thr Uncertain significance ★ ⚠ same type
AARD p.Ala82Val Uncertain significance ★ ⚠ same type
AARD p.Ala83Gly Uncertain significance ★ ⚠ same type
AARD p.Ala85Gly Uncertain significance ★ ⚠ same type
AARD p.Arg103Thr Uncertain significance ★ ⚠ same type
AARD p.Asp150Glu Uncertain significance ★ ⚠ same type
AARD p.Gln130Lys 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/aard-p-val71ala (accessed [today's date]).

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