Is AARD p.Ala70= (c.210G>A) pathogenic?

AARD p.Ala70= (c.210G>A) is classified Benign in AARD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-13). Common (popmax 5.54%, afr) — too common for a highly-penetrant pathogenic allele.

AARD p.Ala70=

Q: How common is AARD p.Ala70= (c.210G>A) in the general population?

AARD p.Ala70= (c.210G>A) is common (popmax 5.54%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.210G>A · rs76753109 · VCV768256

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.54%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.4	GERP -0.78
Overall
CADD	10.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.54% African / African-American · 4,120/74,428 alleles

Filtering AF 5.39% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.34%

Overall 0.293% 4,688/1,601,290 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.54%	18
Admixed American	0.403%	248
Remaining individualsnot grpmax-eligible	0.398%	252
Middle Eastern	0.296%	337
South Asian	0.0223%	4,490
European (non-Finnish)	0.00417%	23,976

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.Ala70=
Coding: c.210G>A
MANE Select: NM_001025357
dbSNP: rs76753109
Type: single nucleotide variant
Location: chr8:116938453 (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.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
AARD p.Gln145Arg 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-ala70 (accessed [today's date]).

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