Is COQ3 p.Phe53Ser (c.158T>C) pathogenic?

COQ3 p.Phe53Ser (c.158T>C) is classified Uncertain significance in COQ3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-28). AlphaMissense: likely benign (0.093); Very rare (popmax 0.00715%, nfe).

How common is COQ3 p.Phe53Ser (c.158T>C) in the general population?

COQ3 p.Phe53Ser (c.158T>C) is very rare (popmax 0.00715%, nfe) (gnomAD).

What do computational predictors say about COQ3 p.Phe53Ser (c.158T>C)?

AlphaMissense predicts likely benign (score 0.093) — an in-silico prediction, not a clinical call.

COQ3 p.Phe53Ser

c.158T>C · VCV3496024

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.093 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00715%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.093	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -5.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP -2.4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 25 kb · p 0.76 · regional, not allelic
Overall
CADD	14.71	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00715% European (non-Finnish) · 84/1,174,338 alleles

Filtering AF 0.0059% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00543%

Overall 0.0055% 88/1,601,210 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00715%	13,980
Remaining individualsnot grpmax-eligible	0.00323%	31,000
Admixed American	0.00172%	58,008
African / African-American	0.00135%	74,272

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: COQ3
Protein: p.Phe53Ser
Coding: c.158T>C
MANE Select: NM_017421
Type: single nucleotide variant
Location: chr6:99383773 (GRCh38)
Gene constraint: LOEUF 1.045 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.17

Full COQ3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COQ3 p.Ala169Pro Uncertain significance ★ ⚠ same type
COQ3 p.Arg197Ile Uncertain significance ★ ⚠ same type
COQ3 p.Arg201Lys Uncertain significance ★ ⚠ same type
COQ3 p.Arg29Cys Uncertain significance ★ ⚠ same type
COQ3 p.Arg29His Uncertain significance ★ ⚠ same type
COQ3 p.Asp109Val Uncertain significance ★ ⚠ same type
COQ3 p.Asp175His Uncertain significance ★ ⚠ same type
COQ3 p.Asp191Asn 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/coq3-p-phe53ser (accessed [today's date]).

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