Is POLRMT p.Pro810Ser (c.2428C>T) pathogenic?

POLRMT p.Pro810Ser (c.2428C>T) is classified Pathogenic in POLRMT (ClinVar, Single submitter, 2 submitters; last evaluated 2025-02-16). AlphaMissense: likely benign (0.1933); Ultra-rare (popmax 0.0442%, nfe); Associated with combined oxidative phosphorylation deficiency 55.

What condition is associated with POLRMT p.Pro810Ser (c.2428C>T)?

POLRMT p.Pro810Ser (c.2428C>T) is associated with combined oxidative phosphorylation deficiency 55 (ClinVar).

How common is POLRMT p.Pro810Ser (c.2428C>T) in the general population?

POLRMT p.Pro810Ser (c.2428C>T) is ultra-rare (popmax 0.0442%, nfe) (gnomAD).

What do computational predictors say about POLRMT p.Pro810Ser (c.2428C>T)?

AlphaMissense predicts likely benign (score 0.1933) — an in-silico prediction, not a clinical call.

POLRMT p.Pro810Ser

c.2428C>T · rs201364510 · VCV1341477

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1933 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0442%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

combined oxidative phosphorylation deficiency 55

Computational evidence

Protein change
AlphaMissense	0.1933	likely benign ⚠ discordant with ClinVar
REVEL	0.183	benign-leaning
SaProt	LLR -10.95	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.3	GERP 0.52, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 16 kb · p 4.5e-11 · regional, not allelic
Overall
CADD	23.4	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 0.0442% European (non-Finnish) · 521/1,177,954 alleles

Filtering AF 0.0411% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0398%

Overall 0.07% 1,125/1,607,446 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.799%	125
Ashkenazi Jewishnot grpmax-eligible	0.228%	439
Remaining individualsnot grpmax-eligible	0.0612%	1,634
European (non-Finnish)grpmax	0.0442%	2,261
Admixed American	0.00669%	14,940
African / African-American	0.00134%	74,858
South Asian	0.0011%	90,870

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: POLRMT
Protein: p.Pro810Ser
Coding: c.2428C>T
MANE Select: NM_005035
dbSNP: rs201364510
Type: single nucleotide variant
Location: chr19:621270 (GRCh38)

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

Disease context

combined oxidative phosphorylation deficiency 55 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/polrmt-p-pro810ser (accessed [today's date]).

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