Is AMER1 p.Ser787Phe (c.2360C>T) pathogenic?

AMER1 p.Ser787Phe (c.2360C>T) is classified Likely benign in AMER1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely pathogenic (0.6411); Very rare (popmax 0.00707%, sas); Associated with Inborn genetic diseases.

What condition is associated with AMER1 p.Ser787Phe (c.2360C>T)?

AMER1 p.Ser787Phe (c.2360C>T) is associated with Inborn genetic diseases (ClinVar).

How common is AMER1 p.Ser787Phe (c.2360C>T) in the general population?

AMER1 p.Ser787Phe (c.2360C>T) is very rare (popmax 0.00707%, sas) (gnomAD).

What do computational predictors say about AMER1 p.Ser787Phe (c.2360C>T)?

AlphaMissense predicts likely pathogenic (score 0.6411) — an in-silico prediction, not a clinical call.

AMER1 p.Ser787Phe

c.2360C>T · VCV4091106

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6411 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00707%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6411	likely pathogenic
REVEL	0.232	benign-leaning
SaProt	LLR -8.89	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 3,404 bp · p 0.037 · regional, not allelic
Overall
CADD	25.0	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 0.00707% South Asian · 4/56,554 alleles

Filtering AF 0.00235% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00141%

Overall 0.000661% 8/1,209,401 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00707%	14,138
Finnishnot grpmax-eligible	0.00644%	15,523
Remaining individualsnot grpmax-eligible	0.0021%	47,587

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: AMER1
Protein: p.Ser787Phe
Coding: c.2360C>T
MANE Select: NM_152424
Type: single nucleotide variant
Location: chrX:64190927 (GRCh38)
Structure: AlphaFold pLDDT 48.88 · 3 PDB

Full AMER1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AMER1 p.Arg353Ter Pathogenic ★★ same condition
AMER1 p.Arg358Ter Pathogenic ★★ same condition
AMER1 p.Ala202Gly Uncertain significance ★★ ⚠ same condition
AMER1 p.Arg1113Met Uncertain significance ★★ ⚠ same condition
AMER1 p.Arg586Gln Uncertain significance ★★ ⚠ same condition
AMER1 p.Arg606Lys Uncertain significance ★★ ⚠ same condition
AMER1 p.Gly1083Val Uncertain significance ★★ ⚠ same condition
AMER1 p.Gly672Glu Uncertain significance ★★ ⚠ same condition

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/amer1-p-ser787phe (accessed [today's date]).

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