Is PHIP p.Ile910Val (c.2728A>G) pathogenic?

PHIP p.Ile910Val (c.2728A>G) is classified Likely benign in PHIP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-09). AlphaMissense: likely benign (0.054); Very rare (popmax 0.00408%, afr).

How common is PHIP p.Ile910Val (c.2728A>G) in the general population?

PHIP p.Ile910Val (c.2728A>G) is very rare (popmax 0.00408%, afr) (gnomAD).

What do computational predictors say about PHIP p.Ile910Val (c.2728A>G)?

AlphaMissense predicts likely benign (score 0.054) — an in-silico prediction, not a clinical call.

PHIP p.Ile910Val

c.2728A>G · VCV4754627

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.054 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00408%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.054	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -5.18	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 -0.67	GERP -4.6, phastCons 0.014
Regional constraint	o/e 0.99	unconstrained · MANE · 4,394 bp · p 0.96 · regional, not allelic
Overall
CADD	6.85	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 0.00408% African / African-American · 3/73,584 alleles

Filtering AF 0.00108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0005%

Overall 0.00044% 7/1,591,514 alleles · very rare exomes 6/1,439,380 · genomes 1/152,134 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00408%	24,528
East Asian	0.00224%	44,674
European (non-Finnish)	0.000256%	390,671

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.Ile910Val
Coding: c.2728A>G
MANE Select: NM_017934
Type: single nucleotide variant
Location: chr6:78982927 (GRCh38)
Gene constraint: LOEUF 0.246 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.57 · 146 PDB
Residue 910: the 'disordered' region; a UniProt-annotated variant site (in chujans)

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

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PHIP p.Arg503Ter Pathogenic/Likely pathogenic ★★ same type
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PHIP p.Asn507Ser Likely pathogenic ★★ ⚠ 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/phip-p-ile910val (accessed [today's date]).

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