Is COX16 p.Ser62Pro (c.184T>C) pathogenic?

COX16 p.Ser62Pro (c.184T>C) is classified Uncertain significance in COX16 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-01). AlphaMissense: ambiguous (0.3908); Ultra-rare (popmax 0.0465%, sas).

How common is COX16 p.Ser62Pro (c.184T>C) in the general population?

COX16 p.Ser62Pro (c.184T>C) is ultra-rare (popmax 0.0465%, sas) (gnomAD).

What do computational predictors say about COX16 p.Ser62Pro (c.184T>C)?

AlphaMissense predicts ambiguous (score 0.3908) — an in-silico prediction, not a clinical call.

COX16 p.Ser62Pro

c.184T>C · rs756535934 · VCV2578720

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3908 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0465%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3908	ambiguous
REVEL	0.082	moderately benign-leaning
SaProt	LLR -11.19	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP -1.4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 33 kb · p 0.75 · 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 0.0465% South Asian · 42/90,292 alleles

Filtering AF 0.0353% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0314%

Overall 0.00597% 96/1,608,434 alleles · ultra-rare exomes 92/1,456,358 · genomes 4/152,076 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0465%	2,150
European (non-Finnish)	0.00459%	21,799

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: COX16
Protein: p.Ser62Pro
Coding: c.184T>C
MANE Select: NM_016468
dbSNP: rs756535934
Type: single nucleotide variant
Location: chr14:70329194 (GRCh38)
Gene constraint: LOEUF 1.373 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.50

Full COX16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COX16 c.141+10A>G Uncertain significance ★ same type
COX16 p.Arg11Leu Uncertain significance ★ ⚠ same type
COX16 p.Arg34His Uncertain significance ★ ⚠ same type
COX16 p.Asn80Asp Uncertain significance ★ ⚠ same type
COX16 p.Gly17Ser Uncertain significance ★ ⚠ same type
COX16 p.Ile70Met Uncertain significance ★ ⚠ same type
COX16 p.Leu56Met Uncertain significance ★ ⚠ same type
COX16 p.Lys14Thr 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/cox16-p-ser62pro (accessed [today's date]).

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