Is ELP4 p.Pro191Gln (c.572C>A) pathogenic?

ELP4 p.Pro191Gln (c.572C>A) is classified Benign/Likely benign in ELP4 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-01). AlphaMissense: likely benign (0.1099); Rare (popmax 0.443%, nfe).

How common is ELP4 p.Pro191Gln (c.572C>A) in the general population?

ELP4 p.Pro191Gln (c.572C>A) is rare (popmax 0.443%, nfe) (gnomAD).

What do computational predictors say about ELP4 p.Pro191Gln (c.572C>A)?

AlphaMissense predicts likely benign (score 0.1099) — an in-silico prediction, not a clinical call.

ELP4 p.Pro191Gln

c.572C>A · rs201699595 · VCV707203

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1099 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.443%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1099	likely benign
REVEL	0.203	benign-leaning
SaProt	LLR -8.96	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 7.6	GERP 2, phastCons 0.94
Regional constraint	o/e 1.01	unconstrained · MANE · 274 kb · p 0.85 · regional, not allelic
Overall
CADD	23.6	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 0.443% European (non-Finnish) · 5,214/1,178,116 alleles

Filtering AF 0.432% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.428%

Overall 0.353% 5,682/1,611,180 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.443%	226
Remaining individualsnot grpmax-eligible	0.247%	405
Admixed American	0.179%	560
Finnishnot grpmax-eligible	0.169%	592
Ashkenazi Jewishnot grpmax-eligible	0.0678%	1,475
African / African-American	0.0667%	1,499
South Asian	0.0319%	3,131

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: ELP4
Protein: p.Pro191Gln
Coding: c.572C>A
MANE Select: NM_019040
dbSNP: rs201699595
Type: single nucleotide variant
Location: chr11:31603826 (GRCh38)
Gene constraint: LOEUF 1.377 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.49

Full ELP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PAX6 p.Arg222Trp Pathogenic/Likely pathogenic ★★ same type
PAX6 p.Ter437Gln Pathogenic/Likely pathogenic ★★ same type
PAX6 p.Ter437Leu Pathogenic/Likely pathogenic ★★ same type
ELP4 p.Arg163His Uncertain significance ★★ ⚠ same type
ELP4 p.Arg31Ser Uncertain significance ★★ ⚠ same type
ELP4 p.Arg395His Uncertain significance ★★ ⚠ same type
ELP4 p.Asn244Ser Uncertain significance ★★ ⚠ same type
ELP4 p.Gln165Pro Uncertain significance ★★ ⚠ 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/elp4-p-pro191gln (accessed [today's date]).

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