Is PTMS p.Pro77= (c.231C>T) pathogenic?

PTMS p.Pro77= (c.231C>T) is classified Likely benign in PTMS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-01). Ultra-rare (popmax 0.0156%, eas).

How common is PTMS p.Pro77= (c.231C>T) in the general population?

PTMS p.Pro77= (c.231C>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

PTMS p.Pro77=

c.231C>T · VCV3940340

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.045	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3	GERP -3.3
Overall
CADD	7.218	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,884 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00514%

Overall 0.00118% 19/1,614,008 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,412
African / African-American	0.00534%	18,727
Finnishnot grpmax-eligible	0.00156%	64,032
European (non-Finnish)	0.000593%	168,574

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: PTMS
Protein: p.Pro77=
Coding: c.231C>T
MANE Select: NM_002824
Type: single nucleotide variant
Location: chr12:6770191 (GRCh38)
Gene constraint: LOEUF 0.627 · pLI 0.82 (gnomAD)
Structure: AlphaFold pLDDT 62.03
Residue 77: the 'disordered' region

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

Similar variants

PTMS p.Pro77Ala Uncertain significance ★ ⚠ same residue
PTMS p.Arg33Gln Uncertain significance ★ ⚠ same type
PTMS p.Asp60Tyr Uncertain significance ★ ⚠ same type
PTMS p.Glu54Asp Uncertain significance ★ ⚠ same type
PTMS p.Val38Met 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/ptms-p-pro77 (accessed [today's date]).

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