Is AMBN p.Ala184Pro (c.550G>C) pathogenic?

AMBN p.Ala184Pro (c.550G>C) is classified Uncertain significance in AMBN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-15). AlphaMissense: likely benign (0.0931); Ultra-rare (popmax 0.0316%, eas).

How common is AMBN p.Ala184Pro (c.550G>C) in the general population?

AMBN p.Ala184Pro (c.550G>C) is ultra-rare (popmax 0.0316%, eas) (gnomAD).

What do computational predictors say about AMBN p.Ala184Pro (c.550G>C)?

AlphaMissense predicts likely benign (score 0.0931) — an in-silico prediction, not a clinical call.

AMBN p.Ala184Pro

c.550G>C · rs772520773 · VCV2601335

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0931 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0316%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0931	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -4.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.4	GERP 0.59, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 14 kb · p 0.31 · regional, not allelic
Overall
CADD	14.1	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 0.0316% East Asian · 14/44,252 alleles

Filtering AF 0.0191% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0153%

Overall 0.00203% 32/1,575,188 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0316%	3,161
South Asian	0.0184%	5,436
Admixed American	0.00177%	56,592
Remaining individualsnot grpmax-eligible	0.00165%	60,712
European (non-Finnish)	8.62e-05%	1,160,312

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: AMBN
Protein: p.Ala184Pro
Coding: c.550G>C
MANE Select: NM_016519
dbSNP: rs772520773
Type: single nucleotide variant
Location: chr4:70602642 (GRCh38)
Gene constraint: LOEUF 1.345 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 44.05
Residue 184: the 'disordered' region

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

Similar variants

AMBN p.Ser70Ter Uncertain significance ★★ same type
AMBN p.Gly268Arg Likely benign ★★ same type
AMBN p.His294Gln Benign/Likely benign ★★ same type
AMBN p.Leu354Pro Benign ★★ same type
AMBN p.Val378Ile Benign ★★ same type
AMBN c.295-2A>C Likely pathogenic ★ same type
AMBN c.15+1G>A Uncertain significance ★ same type
AMBN c.571-1G>C Conflicting classifications of pathogenicity ★ 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/ambn-p-ala184pro (accessed [today's date]).

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