Is AMPH p.Ala484Ser (c.1450G>T) pathogenic?

AMPH p.Ala484Ser (c.1450G>T) is classified Benign in AMPH (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-14). AlphaMissense: likely benign (0.0777); Low-frequency (popmax 2.12%, afr).

How common is AMPH p.Ala484Ser (c.1450G>T) in the general population?

AMPH p.Ala484Ser (c.1450G>T) is low-frequency (popmax 2.12%, afr) (gnomAD).

What do computational predictors say about AMPH p.Ala484Ser (c.1450G>T)?

AlphaMissense predicts likely benign (score 0.0777) — an in-silico prediction, not a clinical call.

AMPH p.Ala484Ser

c.1450G>T · rs73348825 · VCV731328

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0777 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.12%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0777	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	LLR -7.16	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 -0.27	GERP 0.67
Regional constraint	o/e 0.96	unconstrained · MANE · 81 kb · p 0.37 · regional, not allelic
Overall
CADD	7.025	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 2.12% African / African-American · 1,593/75,058 alleles

Filtering AF 2.04% ClinGen BA1/BS1 input FAF95, joint · FAF99 2%

Overall 0.111% 1,793/1,614,242 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.12%	47
Admixed American	0.122%	822
Remaining individualsnot grpmax-eligible	0.122%	823
Middle Eastern	0.099%	1,010
European (non-Finnish)	0.00373%	26,819
South Asian	0.0011%	91,084

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: AMPH
Protein: p.Ala484Ser
Coding: c.1450G>T
MANE Select: NM_001635
dbSNP: rs73348825
Type: single nucleotide variant
Location: chr7:38394163 (GRCh38)
Gene constraint: LOEUF 0.697 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.84 · 6 PDB

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

Similar variants

AMPH c.1017+10T>C Likely benign ★★ same type
AMPH p.Thr586Met Likely benign ★★ same type
AMPH p.Ala10Thr Uncertain significance ★ ⚠ same type
AMPH p.Ala169Gly Uncertain significance ★ ⚠ same type
AMPH p.Ala239Ser Uncertain significance ★ ⚠ same type
AMPH p.Ala248Val Uncertain significance ★ ⚠ same type
AMPH p.Ala284Val Uncertain significance ★ ⚠ same type
AMPH p.Ala287Thr 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/amph-p-ala484ser (accessed [today's date]).

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