Is PHEX p.Ile644Val (c.1930A>G) pathogenic?

PHEX p.Ile644Val (c.1930A>G) is classified Likely benign in PHEX (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-18). AlphaMissense: likely benign (0.1912); Very rare (popmax 0.00177%, afr).

How common is PHEX p.Ile644Val (c.1930A>G) in the general population?

PHEX p.Ile644Val (c.1930A>G) is very rare (popmax 0.00177%, afr) (gnomAD).

What do computational predictors say about PHEX p.Ile644Val (c.1930A>G)?

AlphaMissense predicts likely benign (score 0.1912) — an in-silico prediction, not a clinical call.

PHEX p.Ile644Val

c.1930A>G · rs1180774758 · VCV2082855

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1912 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00177%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1912	likely benign
REVEL	0.652	pathogenic-leaning
SaProt	LLR -8.76	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 215 kb · p 6.8e-05 · regional, not allelic
Overall
CADD	23.1	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 0.00177% African / African-American · 1/56,624 alleles

Overall 8.3e-05% 1/1,204,499 alleles · very rare exomes 1/1,094,143 · genomes 0/110,356 · joint denominator

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: PHEX
Protein: p.Ile644Val
Coding: c.1930A>G
MANE Select: NM_000444
dbSNP: rs1180774758
Type: single nucleotide variant
Location: chrX:22226473 (GRCh38)
Structure: AlphaFold pLDDT 94.58
Residue 644: the peptidase m13 domain

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

Similar variants

PHEX p.Ile644Thr Uncertain significance ★★ ⚠ same residue
PHEX c.1079+1G>A Pathogenic ★★ same type
PHEX c.1079+2T>G Pathogenic ★★ same type
PHEX c.1080-1G>A Pathogenic ★★ same type
PHEX c.1080-2A>G Pathogenic ★★ same type
PHEX c.1080-3C>G Pathogenic ★★ same type
PHEX c.1173+1G>A Pathogenic ★★ same type
PHEX c.1173+2T>C 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/phex-p-ile644val (accessed [today's date]).

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