Is TMEM80 p.Ser26= (c.78C>T) pathogenic?

TMEM80 p.Ser26= (c.78C>T) is classified Likely benign in TMEM80 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-01). Rare (popmax 0.42%, afr).

How common is TMEM80 p.Ser26= (c.78C>T) in the general population?

TMEM80 p.Ser26= (c.78C>T) is rare (popmax 0.42%, afr) (gnomAD).

TMEM80 p.Ser26=

c.78C>T · VCV3770775

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.42%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -8	GERP -2.5
Overall
CADD	0.207	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.42% African / African-American · 315/75,052 alleles

Filtering AF 0.382% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.367%

Overall 0.0285% 460/1,614,130 alleles · rare exomes 262/1,461,818 · genomes 198/152,312 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.42%	238
East Asian	0.123%	816
Remaining individualsnot grpmax-eligible	0.0752%	1,330
Admixed American	0.0333%	3,001
Middle Eastern	0.033%	3,031
South Asian	0.0143%	7,006
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
European (non-Finnish)	0.000593%	168,572

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: TMEM80
Protein: p.Ser26=
Coding: c.78C>T
MANE Select: NM_001042463
Type: single nucleotide variant
Location: chr11:700180 (GRCh38)

Full TMEM80 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/tmem80-p-ser26 (accessed [today's date]).

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