Is AIDA p.Pro208Ser (c.622C>T) pathogenic?

AIDA p.Pro208Ser (c.622C>T) is classified Uncertain significance in AIDA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-21). AlphaMissense: ambiguous (0.4033); Very rare (popmax 0.00401%, afr).

How common is AIDA p.Pro208Ser (c.622C>T) in the general population?

AIDA p.Pro208Ser (c.622C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about AIDA p.Pro208Ser (c.622C>T)?

AlphaMissense predicts ambiguous (score 0.4033) — an in-silico prediction, not a clinical call.

AIDA p.Pro208Ser

c.622C>T · rs764475670 · VCV2387333

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4033 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Computational evidence

Protein change
AlphaMissense	0.4033	ambiguous
REVEL	0.623	indeterminate
SaProt	LLR -9.96	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 42 kb · p 0.028 · regional, not allelic
Overall
CADD	25.6	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 0.00401% African / African-American · 3/74,786 alleles

Filtering AF 0.00165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00199% 32/1,608,878 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,929
European (non-Finnish)	0.00238%	42,042
Admixed American	0.00168%	59,614

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: AIDA
Protein: p.Pro208Ser
Coding: c.622C>T
MANE Select: NM_022831
dbSNP: rs764475670
Type: single nucleotide variant
Location: chr1:222673397 (GRCh38)
Gene constraint: LOEUF 0.545 · pLI 0.93 (gnomAD)
Structure: AlphaFold pLDDT 86.37
Residue 208: the c2 aida-type domain; the 'axin-binding' region

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

Similar variants

AIDA p.Asn51Ser Uncertain significance ★ ⚠ same type
AIDA p.Asp134Tyr Uncertain significance ★ ⚠ same type
AIDA p.Asp186Asn Uncertain significance ★ ⚠ same type
AIDA p.Cys69Arg Uncertain significance ★ ⚠ same type
AIDA p.Glu265Val Uncertain significance ★ ⚠ same type
AIDA p.Glu45Lys Uncertain significance ★ ⚠ same type
AIDA p.Gly198Ser Uncertain significance ★ ⚠ same type
AIDA p.Gly236Asp 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/aida-p-pro208ser (accessed [today's date]).

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