Is ARMC12 p.Pro50Ser (c.148C>T) pathogenic?

ARMC12 p.Pro50Ser (c.148C>T) is classified Uncertain significance in ARMC12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-02). AlphaMissense: likely benign (0.3278); Absent from gnomAD v4.1.

How common is ARMC12 p.Pro50Ser (c.148C>T) in the general population?

ARMC12 p.Pro50Ser (c.148C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARMC12 p.Pro50Ser (c.148C>T)?

AlphaMissense predicts likely benign (score 0.3278) — an in-silico prediction, not a clinical call.

ARMC12 p.Pro50Ser

c.148C>T · VCV3947499

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3278 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3278	likely benign
REVEL	0.333	indeterminate
SaProt	LLR -5.56	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 12 kb · p 0.039 · regional, not allelic
Overall
CADD	25.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARMC12
Protein: p.Pro50Ser
Coding: c.148C>T
MANE Select: NM_001286574
Type: single nucleotide variant
Location: chr6:35737256 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.08
Residue 50: the 'interaction with tbc1d15' region

Full ARMC12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARMC12 c.163+10C>T Uncertain significance ★ same type
ARMC12 c.163+19G>C Uncertain significance ★ same type
ARMC12 c.163+38G>C Uncertain significance ★ same type
ARMC12 c.163+52C>G Uncertain significance ★ same type
ARMC12 c.163+54G>A Uncertain significance ★ same type
ARMC12 p.Ala104Val Uncertain significance ★ ⚠ same type
ARMC12 p.Ala27Val Uncertain significance ★ ⚠ same type
ARMC12 p.Ala37Ser 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/armc12-p-pro50ser (accessed [today's date]).

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