Is AMTN p.Ser50Pro (c.148T>C) pathogenic?

AMTN p.Ser50Pro (c.148T>C) is classified Benign in AMTN (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-03-19). AlphaMissense: likely benign (0.1343); Common (popmax 7.26%, afr) — too common for a highly-penetrant pathogenic allele; Associated with AMTN-related disorder.

What condition is associated with AMTN p.Ser50Pro (c.148T>C)?

AMTN p.Ser50Pro (c.148T>C) is associated with AMTN-related disorder (ClinVar).

What do computational predictors say about AMTN p.Ser50Pro (c.148T>C)?

AlphaMissense predicts likely benign (score 0.1343) — an in-silico prediction, not a clinical call.

AMTN p.Ser50Pro

Q: How common is AMTN p.Ser50Pro (c.148T>C) in the general population?

AMTN p.Ser50Pro (c.148T>C) is common (popmax 7.26%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.148T>C · rs34803339 · VCV3042027

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1343 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 7.26%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

AMTN-related disorder

Computational evidence

Protein change
AlphaMissense	0.1343	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -5.77	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 1.8, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 14 kb · p 0.91 · regional, not allelic
Overall
CADD	22.1	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 7.26% African / African-American · 5,445/74,992 alleles

Filtering AF 7.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.03%

Overall 0.614% 9,906/1,613,634 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.26%	14
South Asian	3.71%	27
Remaining individualsnot grpmax-eligible	0.754%	133
Middle Eastern	0.66%	151
Admixed American	0.625%	160
European (non-Finnish)	0.016%	6,242
East Asian	0.0156%	6,409
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,600

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: AMTN
Protein: p.Ser50Pro
Coding: c.148T>C
MANE Select: NM_212557
dbSNP: rs34803339
Type: single nucleotide variant
Location: chr4:70523877 (GRCh38)
Gene constraint: LOEUF 1.656 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 48.75
Residue 50: a UniProt-annotated variant site (in)

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

Disease context

AMTN-related disorder

Similar variants

AMTN c.205-7C>T Benign same condition
AMTN c.-7C>T Benign same condition
AMTN p.Arg15Trp Benign same condition
AMTN p.Gly88Glu Likely benign same condition
AMTN p.Gly177Val Benign ★★ same type
AMTN p.Ala155Thr Uncertain significance ★ ⚠ same type
AMTN p.Ala188Ser Uncertain significance ★ ⚠ same type
AMTN p.Ala205Thr 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/amtn-p-ser50pro (accessed [today's date]).

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