Is AAMDC p.Thr2Ser (c.4A>T) pathogenic?

AAMDC p.Thr2Ser (c.4A>T) is classified Likely benign in AAMDC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: likely benign (0.0624); Absent from gnomAD v4.1.

How common is AAMDC p.Thr2Ser (c.4A>T) in the general population?

AAMDC p.Thr2Ser (c.4A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AAMDC p.Thr2Ser (c.4A>T)?

AlphaMissense predicts likely benign (score 0.0624) — an in-silico prediction, not a clinical call.

AAMDC p.Thr2Ser

c.4A>T · VCV4213536

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0624 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0624	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -2.91	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 0.99	GERP -2.3, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 30 kb · p 0.75 · regional, not allelic
Overall
CADD	6.493	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AAMDC
Protein: p.Thr2Ser
Coding: c.4A>T
MANE Select: NM_024684
Type: single nucleotide variant
Location: chr11:77842500 (GRCh38)
Gene constraint: LOEUF 1.571 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.78 · 2 PDB
Residue 2: an α-helix

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

Similar variants

AAMDC p.Arg34Trp Uncertain significance ★ ⚠ same type
AAMDC p.Arg69Gln Uncertain significance ★ ⚠ same type
AAMDC p.Glu40Lys Uncertain significance ★ ⚠ same type
AAMDC p.Gly12Glu Uncertain significance ★ ⚠ same type
AAMDC p.Gly18Ala Uncertain significance ★ ⚠ same type
AAMDC p.Gly31Ala Uncertain significance ★ ⚠ same type
AAMDC p.Gly48Arg Uncertain significance ★ ⚠ same type
AAMDC p.Gly61Arg 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/aamdc-p-thr2ser (accessed [today's date]).

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