Is PHC1 p.Arg306= (c.918A>G) pathogenic?

PHC1 p.Arg306= (c.918A>G) is classified Benign in PHC1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2021-09-05). Common (popmax 96.4%, sas) — too common for a highly-penetrant pathogenic allele; Associated with microcephaly 11, primary, autosomal recessive.

What condition is associated with PHC1 p.Arg306= (c.918A>G)?

PHC1 p.Arg306= (c.918A>G) is associated with microcephaly 11, primary, autosomal recessive (ClinVar).

PHC1 p.Arg306=

Q: How common is PHC1 p.Arg306= (c.918A>G) in the general population?

PHC1 p.Arg306= (c.918A>G) is common (popmax 96.4%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.918A>G · rs1805777 · VCV211899

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 96.4%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

microcephaly 11, primary, autosomal recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP -0.12, phastCons 1
Overall
CADD	10.03	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 96.4% South Asian · 64,293/66,700 alleles

Filtering AF 95.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 95.5%

Overall 92.3% 1,097,284/1,188,302 alleles · common exomes 972,484/1,042,370 · genomes 124,800/145,932 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	96.4%	1
Finnishnot grpmax-eligible	96%	1
Amishnot grpmax-eligible	95%	1
European (non-Finnish)	95%	1
Ashkenazi Jewishnot grpmax-eligible	92%	1
Remaining individualsnot grpmax-eligible	90.9%	1
Middle Eastern	90.7%	1
Admixed American	89.7%	1
East Asian	76.9%	1
African / African-American	62.2%	2

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: PHC1
Protein: p.Arg306=
Coding: c.918A>G
MANE Select: NM_004426
dbSNP: rs1805777
Type: single nucleotide variant
Location: chr12:8930740 (GRCh38)
Gene constraint: LOEUF 0.322 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 51.06 · 1 PDB
Residue 306: the 'disordered' region

Full PHC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

microcephaly 11, primary, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PHC1 p.Arg876Trp Uncertain significance ★★ ⚠ same condition
PHC1 c.2860+12C>T Benign ★★ same condition
PHC1 p.Leu31= Benign ★★ same condition
PHC1 p.Pro123= Benign ★★ same condition
PHC1 p.Thr693Ala Benign ★★ same condition
PHC1 p.Arg34Ter Pathogenic ★ same condition
PHC1 p.Met593Leu Uncertain significance ★ ⚠ same condition
PHC1 p.Pro24Leu Uncertain significance ★ ⚠ same condition

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/phc1-p-arg306 (accessed [today's date]).

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