Is PHIP p.Ile1085= (c.3255C>A) pathogenic?

PHIP p.Ile1085= (c.3255C>A) is classified Likely benign in PHIP (ClinVar, Single submitter, 2 submitters; last evaluated 2023-03-08). Very rare (popmax 0.00267%, afr).

How common is PHIP p.Ile1085= (c.3255C>A) in the general population?

PHIP p.Ile1085= (c.3255C>A) is very rare (popmax 0.00267%, afr) (gnomAD).

PHIP p.Ile1085=

c.3255C>A · rs1269812345 · VCV2787895

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

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 2.7	GERP -1.2, phastCons 1
Overall
CADD	7.652	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,896 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,613,582 alleles · very rare exomes 1/1,461,466 · genomes 2/152,116 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,448
South Asian	0.0011%	91,052

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: PHIP
Protein: p.Ile1085=
Coding: c.3255C>A
MANE Select: NM_017934
dbSNP: rs1269812345
Type: single nucleotide variant
Location: chr6:78966007 (GRCh38)

Full PHIP 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/phip-p-ile1085 (accessed [today's date]).

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