Is AMD1 p.Ser171Thr (c.512G>C) pathogenic?

AMD1 p.Ser171Thr (c.512G>C) is classified Uncertain significance in AMD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-07). AlphaMissense: likely benign (0.0659); Very rare (popmax 8.47e-05%, nfe).

How common is AMD1 p.Ser171Thr (c.512G>C) in the general population?

AMD1 p.Ser171Thr (c.512G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about AMD1 p.Ser171Thr (c.512G>C)?

AlphaMissense predicts likely benign (score 0.0659) — an in-silico prediction, not a clinical call.

AMD1 p.Ser171Thr

c.512G>C · VCV3534792

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0659 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0659	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -4.44	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 1.3	GERP 0.94, phastCons 0.99
Regional constraint	o/e 0.65	unconstrained · MANE · 4,672 bp · p 1.3e-09 · regional, not allelic
Overall
CADD	12.91	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 8.47e-05% European (non-Finnish) · 1/1,180,038 alleles

Overall 6.84e-05% 1/1,461,236 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: AMD1
Protein: p.Ser171Thr
Coding: c.512G>C
MANE Select: NM_001634
Type: single nucleotide variant
Location: chr6:110892340 (GRCh38)
Gene constraint: LOEUF 0.442 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 93.52 · 28 PDB
Residue 171: an α-helix

Full AMD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDK19 p.Thr31Asn Pathogenic/Likely pathogenic ★★ same type
CDK19 p.Gly28Ala Likely pathogenic ★ same type
CDK19 p.Gly28Arg Pathogenic ★ same type
CDK19 p.Tyr32His Pathogenic ★ same type
AMD1 p.Arg168Gln Uncertain significance ★ ⚠ same type
AMD1 p.Arg210Cys Uncertain significance ★ ⚠ same type
AMD1 p.Arg210His Uncertain significance ★ ⚠ same type
AMD1 p.Arg269Gly 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/amd1-p-ser171thr (accessed [today's date]).

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