Is DDA1 p.Ala21Val (c.62C>T) pathogenic?

DDA1 p.Ala21Val (c.62C>T) is classified Uncertain significance in DDA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-13). AlphaMissense: ambiguous (0.3512); Very rare (popmax 0.00576%, nfe).

How common is DDA1 p.Ala21Val (c.62C>T) in the general population?

DDA1 p.Ala21Val (c.62C>T) is very rare (popmax 0.00576%, nfe) (gnomAD).

What do computational predictors say about DDA1 p.Ala21Val (c.62C>T)?

AlphaMissense predicts ambiguous (score 0.3512) — an in-silico prediction, not a clinical call.

DDA1 p.Ala21Val

c.62C>T · rs372277903 · VCV3080693

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3512 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00576%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3512	ambiguous
REVEL	0.215	benign-leaning
SaProt	LLR -6.13	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.52	unconstrained · MANE · 6,332 bp · p 1.5e-05 · regional, not allelic
Overall
CADD	23.1	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 0.00576% European (non-Finnish) · 68/1,180,020 alleles

Filtering AF 0.00462% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00422%

Overall 0.00452% 73/1,613,980 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00576%	17,353
Admixed American	0.00333%	30,003
African / African-American	0.00267%	37,464
East Asian	0.00223%	44,892

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: DDA1
Protein: p.Ala21Val
Coding: c.62C>T
MANE Select: NM_024050
dbSNP: rs372277903
Type: single nucleotide variant
Location: chr19:17314081 (GRCh38)
Gene constraint: LOEUF 0.455 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 67.25 · 30 PDB

Full DDA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDA1 p.Ala91Val Uncertain significance ★ ⚠ same type
DDA1 p.Arg31Gln Uncertain significance ★ ⚠ same type
DDA1 p.Arg31Trp Uncertain significance ★ ⚠ same type
DDA1 p.Asn67Tyr Uncertain significance ★ ⚠ same type
DDA1 p.Asp101Tyr Uncertain significance ★ same type
DDA1 p.Asp22Asn Uncertain significance ★ ⚠ same type
DDA1 p.Glu100Lys Uncertain significance ★ ⚠ same type
DDA1 p.Glu82Asp 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/dda1-p-ala21val (accessed [today's date]).

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