Is COX7B p.Ser16Arg (c.48C>A) pathogenic?

COX7B p.Ser16Arg (c.48C>A) is classified Benign in COX7B (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-17). AlphaMissense: ambiguous (0.3446); Low-frequency (popmax 2.9%, afr).

How common is COX7B p.Ser16Arg (c.48C>A) in the general population?

COX7B p.Ser16Arg (c.48C>A) is low-frequency (popmax 2.9%, afr) (gnomAD).

What do computational predictors say about COX7B p.Ser16Arg (c.48C>A)?

AlphaMissense predicts ambiguous (score 0.3446) — an in-silico prediction, not a clinical call.

COX7B p.Ser16Arg

c.48C>A · rs61752458 · VCV381408

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.3446 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.9%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3446	ambiguous
REVEL	0.133	moderately benign-leaning
SaProt	LLR -8.23	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.98	GERP -0.27, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 5,704 bp · p 0.27 · regional, not allelic
Overall
CADD	19.98	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 2.9% African / African-American · 1,661/57,254 alleles

Filtering AF 2.78% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.74%

Overall 0.164% 1,976/1,207,750 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.9%	34
Admixed American	0.291%	343
Remaining individualsnot grpmax-eligible	0.225%	444
Middle Eastern	0.224%	446
South Asian	0.0123%	8,100
European (non-Finnish)	0.00682%	14,668

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: COX7B
Protein: p.Ser16Arg
Coding: c.48C>A
MANE Select: NM_001866
dbSNP: rs61752458
Type: single nucleotide variant
Location: chrX:77902650 (GRCh38)
Structure: AlphaFold pLDDT 90.15 · 3 PDB

Full COX7B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COX7B p.Arg29His Uncertain significance ★★ ⚠ same type
COX7B c.165+10A>G Benign ★★ same type
COX7B c.*82G>T Likely benign ★★ same type
COX7B c.40+5G>C Likely pathogenic ★ same type
COX7B p.Ala57Ser Uncertain significance ★ ⚠ same type
COX7B p.Asn79Asp Uncertain significance ★ ⚠ same type
COX7B p.Leu66Val Uncertain significance ★ ⚠ same type
COX7B p.Lys36Arg Conflicting classifications of pathogenicity ★ ⚠ 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/cox7b-p-ser16arg (accessed [today's date]).

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