Is MED17 p.Pro337= (c.1011G>A) pathogenic?

MED17 p.Pro337= (c.1011G>A) is classified Benign/Likely benign in MED17 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-28). Rare (popmax 0.258%, amr); Associated with infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly.

How common is MED17 p.Pro337= (c.1011G>A) in the general population?

MED17 p.Pro337= (c.1011G>A) is rare (popmax 0.258%, amr) (gnomAD).

MED17 p.Pro337=

Q: What condition is associated with MED17 p.Pro337= (c.1011G>A)?

MED17 p.Pro337= (c.1011G>A) is associated with infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly (ClinVar).

c.1011G>A · rs141529021 · VCV771893

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.258%, amr)

Conditions

infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.2	GERP -3.3, phastCons 1
Overall
CADD	10.61	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.258% Admixed American · 155/60,020 alleles

Filtering AF 0.225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.212%

Overall 0.107% 1,730/1,614,074 alleles · rare exomes 1,574/1,461,832 · genomes 156/152,242 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.258%	387
European (non-Finnish)	0.124%	805
Remaining individualsnot grpmax-eligible	0.115%	868
Ashkenazi Jewishnot grpmax-eligible	0.0338%	2,960
African / African-American	0.0333%	3,000
East Asian	0.00446%	22,431
Finnishnot grpmax-eligible	0.00156%	64,006

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: MED17
Protein: p.Pro337=
Coding: c.1011G>A
MANE Select: NM_004268
dbSNP: rs141529021
Type: single nucleotide variant
Location: chr11:93795059 (GRCh38)
Gene constraint: LOEUF 0.719 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.95 · 11 PDB

Full MED17 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MED17 p.Pro337Leu Uncertain significance ★★ ⚠ same residue
MED17 c.1013-1G>A Likely pathogenic ★★ same condition
MED17 c.1467-1G>C Likely pathogenic ★★ same condition
MED17 c.1585-1G>T Likely pathogenic ★★ same condition
MED17 p.Arg189Ter Pathogenic/Likely pathogenic ★★ same condition
MED17 p.Arg197Ter Pathogenic/Likely pathogenic ★★ same condition
MED17 p.Arg279Ter Pathogenic/Likely pathogenic ★★ same condition
MED17 p.Arg454Ter Pathogenic/Likely pathogenic ★★ 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/med17-p-pro337 (accessed [today's date]).

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