Is APOH p.Cys264Phe (c.791G>T) pathogenic?

APOH p.Cys264Phe (c.791G>T) is classified Uncertain significance in APOH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-27). AlphaMissense: likely pathogenic (0.978); Very rare (popmax 0.00223%, eas).

How common is APOH p.Cys264Phe (c.791G>T) in the general population?

APOH p.Cys264Phe (c.791G>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about APOH p.Cys264Phe (c.791G>T)?

AlphaMissense predicts likely pathogenic (score 0.978) — an in-silico prediction, not a clinical call.

APOH p.Cys264Phe

c.791G>T · rs1228626247 · VCV3128015

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.978 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.978	likely pathogenic · top 6% in APOH
REVEL	0.934	strongly pathogenic-leaning
SaProt	LLR -14.50	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.4, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 4,684 bp · p 0.37 · regional, not allelic
Overall
CADD	29.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00223% East Asian · 1/44,764 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00149% 24/1,610,518 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,764
European (non-Finnish)	0.00187%	53,545
Admixed American	0.00168%	59,498

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: APOH
Protein: p.Cys264Phe
Coding: c.791G>T
MANE Select: NM_000042
dbSNP: rs1228626247
Type: single nucleotide variant
Location: chr17:66214644 (GRCh38)
Gene constraint: LOEUF 1.542 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.16 · 14 PDB
Residue 264: a disulfide bond; the 'sushi-like' region

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

Similar variants

APOH c.64+8C>T Benign ★★ same type
APOH p.Ala160Asp Benign ★★ same type
APOH p.Arg154His Benign ★★ same type
APOH p.Asn75Ser Benign ★★ same type
APOH p.Pro53= Benign ★★ same type
APOH p.Ala170Thr Uncertain significance ★ ⚠ same type
APOH p.Ala179Val Uncertain significance ★ ⚠ same type
APOH p.Ala230Thr 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/apoh-p-cys264phe (accessed [today's date]).

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